| Summary of the eRumor: The eRumor talks of a substance called "laminin" that is described as part of a family of proteins that "hold us together." Then there is a picture of laminin---which looks like a cross. |
| The Truth: This story leads into complex considerations of science and biology but the main questions it prompts are whether laminin is as important as the eRumor claims and does it have a shape like a cross. The simple answer to both questions seems to be yes. Laminin is defined by the Webster Medical Dictionary as a "glycoprotein that is a component of connective tissue basement membrane and that promotes cell adhesion." In other words, looking at laminin as a kind of glue isn't far from the truth. There are several different laminins. In their book The Laminins authors Peter Elkblom and Rupert Timpl go into more detail about both the importance of laminins and their structure. They describe laminins that, together with other proteins, "hold cells and tissues together." They also say, "Electron microscopy reveals a cross-like shape for all laminins investigated so far." They went on to say that in solution the laminin shapes were more like a flower than a cross. The strands of laminins do not always stand straight and at right angles, but they do consists of arms, three of which are short and one of which is long. Research has been conducted on laminins in connection with numerous conditions and diseases. It has been found, for example, that people with congenital muscular dystrophies do not have laminin-alpha2, which is normally found in the layer of cells around muscle fibers and other cells important to the structural integrity of muscle cells. Updated 5/14/08 |
| A real example of the eRumor as it has appeared on the Internet: |
| A couple of days ago I was running (I use that term very loosely) on my treadmill, watching a DVD sermon by Louie Giglio...and I was BLOWN AWAY! I want to share what I learned....but I fear not being able to convey it as well as I want. I will share anyway. He (Louie) was talking about how inconceivably BIG our God is...how He spoke the universe into being...how He breathes stars out of His mouth that are huge raging balls of fire...etc. etc. Then He went on to speak of how this star-breathing, universe creating God ALSO knitted our human bodies together with amazing detail and wonder. At this point I am LOVING it (fascinating from a medical standpoint, you know.) .....and I was remembering how I was constantly amazed during medical school as I learned more and more about God's handiwork. I remember so many times thinking...."How can ANYONE deny that a Creator did all of this???" Louie went on to talk about how we can trust that the God who created all this, also has the power to hold it all together when things seem to be falling apart...how our loving Creator is also our sustainer. And then I lost my breath. And it wasn't because I was running my treadmill, either!!! It was because he started talking about laminin. I knew about laminin. Here is how wikipedia describes them :"Laminins are a family of proteins that are an integral part of the structural scaffolding of basement membranes in almost every animal tissue." You see....laminins are what hold us together....LITERALLY. They are cell adhesion molecules. They are what holds one cell of our bodies to the next cell. Without them, we would literally fall apart. And I knew all this already. But what I didn't know is what laminin LOOKED LIKE. But now I do. And I have thought about it a thousand times since (already).... Here is what the structure of laminin looks like...AND THIS IS NOT a "Christian portrayal" of it....if you look up laminin in any scientific/medical piece of literature, this is what you will see...  Now tell me that our God is not the coolest!!! Amazing. The glue that holds us together....ALL of us....is in the shape of the cross. Immediately Colossians 1:15-17 comes to mind. "He is the image of the invisible God, the firstborn over all creation. For by him all things were created; things in heaven and on earth , visible and invisible, whether thrones or powers or rulers or authorities; all things were created by him and for him. He is before all things, and in him all things HOLD TOGETHER. " Colossians 1:15-17 Call me crazy. I just think that is very, very, very cool. Thousands of years before the world knew anything about laminin, Paul penned those words. And now we see that from a very LITERAL standpoint, we are held together...one cell to another....by the cross. You would never in a quadrillion years convince me that is anything other than the mark of a Creator who knew EXACTLY what laminin "glue" would look like long before Adam even breathed his first breath!! Praise the Lord!!!!!!!!!!!!!!!!!! |
Researchers illuminate laminin's role in cancer formation
by Lynn Yarris
EnlargeA 3D cell culture assay developed by Mina Bissell and her research group enables breast cells to reproduce actual structural units, an advantage that was essential for understanding the role of laminin in breast cancer development. (Image from Bissell group)
Laminin, long thought to be only a structural support protein in the microenvironment of breast and other epithelial tissue, is “famous” for its cross-like shape. However, laminin is far more than just a support player with a “pretty face.” Two studies led by one of the world’s foremost breast cancer scientists have shown how laminin plays a central role in the development of breast cancer, the second most leading cause of cancer death among women in the United States. In one study it was shown how laminin influences the genetic information inside a cell’s nucleus. In the other study it was shown how destruction of laminin can play a detrimental role in the early stages of tumor development.
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Mina Bissell holds the title of “Distinguished Scientist” with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab). She herself is famous for having discovered the critical role in breast cancer development played by the extracellular matrix (ECM), the network of fibrous and globular proteins surrounding a breast cell. Her “dynamic reciprocity” theory holds that the fate of cells – whether they stay healthy or become cancerous – hinges on the chemical signals exchanged between the ECM and a cell’s nucleus. In these latest studies, Bissell and her collaborators focused on laminin and its connections with two other proteins – actin, a cytoplasmic protein that has been linked to nuclear activities; and MMP9, an enzyme that is secreted outside the cells and is known to break down ECM constituents.
Laminin and Cell Quiescence
“Quiescence” is the process by which a biological cell stops growing or dividing. This is the opposite of a cancerous state, in which cell growth and division is often unchecked. Signals from laminin-111, an ECM protein that helps the cell and its ECM stick together, have been linked to cell quiescence but the mechanism was unknown. Bissell and postdoctoral fellow, Virginia Spencer, in Berkeley Lab’s Life Sciences Division, have now shown that the addition of laminin-111 leads to quiescence in breast epithelial cells through changes in nuclear actin.
“We found that high levels of laminin-111 depleted nuclear actin and this in turn induced cell quiescence,” Bissell says. “Furthermore, this process can be prevented if a form of actin that can not exit the nucleus is introduced. Under these conditions the cells do not stop growing even in the presence of laminin.”
In their study, Bissell and Spencer and their colleagues used a unique three-dimensional cell culture assay developed by Bissell’s research group, and worked with mouse and human mammary epithelial cells. Through the addition of laminin-111, they were able to decrease nuclear actin levels in the cultured cells, which reduced DNA synthesis and transcription. When nuclear actin levels were deliberately over-expressed, the effects were reversed and cells were prevented from becoming quiescent even in the presence of laminin-111. Furthermore, the high levels of nuclear actin were concentrated in regions of the breast cells where there was little or no laminin-111. Taken together, the results implicate laminin-111 as the regulator of nuclear actin and nuclear actin as a key mediator of epithelial cell quiescence.
Laminin is famous for being shaped like a cross but it should be valued for its role in preventing cancer development. (Image from National Institutes of Health)
“In collaboration with Ole Petersen’s laboratory, we had found previously that the ECM surrounding tissues from breast cancers has a dramatic reduction in laminin-111 in comparison to the ECM surrounding a normal breast cell, which is rich in laminin-111,” Bissell says. “However, just giving laminin back to cancer cells was not enough to make them normal so other factors are clearly also involved and one such factor we now know is how laminin-111 and nuclear actin talk to each other!”
Says Spencer, “Ours is the first study to actually identify laminin-111 as the physiological regulator of nuclear actin and to implicate the loss of nuclear actin as a key step in reaching quiescence and homeostasis in the mammary gland in vivo and in culture.”
Spencer believes that the interaction between laminin-111 and nuclear actin could provide a new target for diagnostic therapeutic efforts, but this will require further study.
“While it remains to be determined whether dysregulation of the levels or organization of nuclear actin is responsible for the inability of malignant cells to respond to growth-inhibitory signals from laminin-111, our preliminary results point in this direction,” she says. “In addition, the findings that laminin-111 expression is lost in myoepithelial cells isolated from human tumors should place the interaction of laminin-111 and breast tumor cells at the forefront of future investigations.”
A paper detailing the results of this study appears in the Journal of Cell Science. The paper is titled “Depletion of nuclear actin is a key mediator of quiescence in epithelial cells.” Co-authoring the paper with Bissell and Spencer were Sylvain Costes, Jamie Inman, Ren Xu, James Chen and Michael Hendzel.
Laminin, MMP9 and Tumor Growth
In the second study, which was related to the role of laminin-111 in cell quiescence, Bissell and another group of collaborators examined laminin-111 in the context of matrix metalloproteinase-9 (MMP9), a zinc-dependent enzyme that plays a huge role in tissue function by virtue of its ability to cleave or degrade many of the ECM constituent proteins, including laminin-111.
“Organization into polarized three-dimensional tissue structures defines whether epithelial cells are normal or malignant,” Bissell says. “We have shown that when MMP9 degrades laminin-111 in the ECM, the tissue architecture of breast cells becomes lost and cell proliferation is initiated. This is the first demonstration of how the degradation of laminin-111 by MMP9 in a physiological context contributes to tumor progression.”
A paper detailing the results of this study has appeared in the journal Genes and Development. The paper is titled “Raf-induced MMP9 Disrupts Tissue Architecture of Human Breast Cells in Three-Dimensional Culture and is Necessary for Tumor Growth in vivo.” Co-authoring the paper with Bissell were Alain Beliveau, Joni Mott, Alvin Lo, Emily Chen, Antonius Koller, Paul Yaswen and John Muschler.
Using a model of human breast cancer where breast epithelial cells were grown in three-dimensional cultures of basement membrane, a thin layer of ECM material that envelops breast and other glandular tissue, Bissell and her co-authors found that not only did excessive MMP9 activity disrupt tissue architecture, but that silencing MMP9 restored tissue architecture and decreased the ability of human beast cancer cells to form tumors in mice.
“We found that in all conditions where tumor cells could be reverted to a normal phenotype in our 3D assays, a novel signaling loop through a pathway of Raf/MEK/ERK proteins was responsible for MMP9 activity in the breast tumor cells,” says co-author Joni Mott, a researcher with Bissell’s group in Berkeley Lab’s Life Sciences Division. “Once MMP9 was activated, the proteinase targeted the destruction of laminin-111 within the basement membrane.”
Laminin-111 in the basement membrane, Mott explains, allows mammary epithelial cells to establish a normal polarized structural unit called an “acinus,” which is responsible for storing milk and making it available for babies when they suckle.
In their Genes and Development paper, Bissell, Mott and their co-authors reported that when the integrity of the tissue architecture was compromised by laminin proteolysis, the basement membrane no longer provided the appropriate signals to restrain epithelial cell proliferation. The result was a sustained signaling of the Raf/MEK/ERK pathway that leads to continued MMP9 production and further disruption of tissue architecture and loss of cell growth control.
“This work is particularly poignant because it provides potential new therapeutic targets for controlling breast cancer and revitalizes the possibility of targeting MMPs in cancer therapy,” Bissell says. “New information on how MMP9 and other MMPs truly function may provide highly targeted and effective therapeutic strategies to control MMP activity in cancer, and may soon lead to the development of novel cancer treatments.”
Both studies were funded in part by grants from the U.S. Department of Energy’s Office of Science, the National Cancer Institute, and the U.S. Department of Defense.
Provided by Lawrence Berkeley National Laboratory (news : web)
Laminin
Glurge: Narrative marvels at the cross-like shape of the laminin molecule.
Example: [Collected via e-mail, May 2008]
Origins: The New Testament's book of Colossians (one of the thirteen epistles traditionally attributed to Paul, this one addressed to Christians in the city Colossae) reads as follows (in verses 1:12-20 of the King James Version):
It is not uncommon for sermons and other Christian devotional/inspirational writings to cite this passage in comparison with some scientific concept: Just as gravity or atoms or molecules are the "glue" that holds the physical world together, so God or Jesus is the force that binds the spiritual world. The example involving laminin glycoprotein cited above is one example of this form, with the addition of a graphic meant to illustrate how God's design is evident (in the shape of a cross) in the molecular structure of laminin — what literally holds us together (in a biological sense) was clearly created by He who spiritually holds us together. This particular example is based on the work of Christian pastor/evangelist Louie Giglio, as seen in the following video clip:
Discussions about whether or not nature evinces signs of a purposeful (Christian) creator are theological/scientific debates that can (and do) fill volumes, so we'll just note a few items to consider:
Example: [Collected via e-mail, May 2008]
A couple of days ago I was running (I use that term very loosely) on my treadmill, watching a DVD sermon by Louie Giglio ... and I was BLOWN AWAY! I want to share what I learned ... but I fear not being able to convey it as well as I want. I will share anyway. He (Louie) was talking about how inconceivably BIG our God is ... how He spoke the universe into being ... how He breathes stars out of His mouth that are huge raging balls of fire ... etc. etc. Then He went on to speak of how this star-breathing, universe creating God ALSO knitted our human bodies together with amazing detail and wonder. At this point I am LOVING it (fascinating from a medical standpoint, you know.) ... and I was remembering how I was constantly amazed during medical school as I learned more and more about God's handiwork. I remember so many times thinking ... "How can ANYONE deny that a Creator did all of this???" Louie went on to talk about how we can trust that the God who created all this, also has the power to hold it all together when things seem to be falling apart ... how our loving Creator is also our sustainer. And then I lost my breath. And it wasn't because I was running my treadmill, either!!! It was because he started talking about laminin. I knew about laminin. Here is how wikipedia describes them: "Laminins are a family of proteins that are an integral part of the structural scaffolding of basement membranes in almost every animal tissue." You see ... laminins are what hold us together ... LITERALLY. They are cell adhesion molecules. They are what holds one cell of our bodies to the next cell. Without them, we would literally fall apart. And I knew all this already. But what I didn't know is what laminin LOOKED LIKE. But now I do. And I have thought about it a thousand times since (already) ... Here is what the structure of laminin looks like ... AND THIS IS NOT a "Christian portrayal" of it ... if you look up laminin in any scientific/medical piece of literature, this is what you will see ...  Now tell me that our God is not the coolest!!! Amazing! The 'glue' that holds us together ... ALL of us ... is in the shape of the cross. Immediately Colossians 1:15-17 comes to mind. "He is the image of the invisible God, the firstborn over all creation. For by him all things were created; things in heaven and on earth , visible and invisible, whether thrones or powers or rulers or authorities; all things were created by him and for him. He is before all things, and in him all things HOLD TOGETHER." Colossians 1:15-17 Call me crazy. I just think that is very, very, very cool. Thousands of years before the world knew anything about laminin, Paul penned those words. And now we see that from a very LITERAL standpoint, we are held together...one cell to another....by the cross. You would never in a quadrillion years convince me that is anything other than the mark of a Creator who knew EXACTLY what laminin "glue" would look like long before Adam even breathed his first breath!! We praise YOU, Lord!!!!!!!!!!!!!!!!!! |
Giving thanks unto the Father, which hath made us meet to be partakers of the inheritance of the saints in
light:
Who hath delivered us from the power of darkness, and hath translated us into the kingdom of his dear Son:
In whom we have redemption through his blood, even the forgiveness of sins:
Who is the image of the invisible God, the firstborn of every creature:
For by him were all things created, that are in heaven, and that are in earth, visible and invisible, whether they be thrones, or dominions, or principalities, or powers: all things were created by him, and for him:
And he is before all things, and by him all things consist.
And he is the head of the body, the church: who is the beginning, the firstborn from the dead; that in all things he might have the preeminence.
For it pleased the Father that in him should all fullness dwell;
And, having made peace through the blood of his cross, by him to reconcile all things unto himself; by him, I say, whether they be things in earth, or things in heaven.
Who hath delivered us from the power of darkness, and hath translated us into the kingdom of his dear Son:
In whom we have redemption through his blood, even the forgiveness of sins:
Who is the image of the invisible God, the firstborn of every creature:
For by him were all things created, that are in heaven, and that are in earth, visible and invisible, whether they be thrones, or dominions, or principalities, or powers: all things were created by him, and for him:
And he is before all things, and by him all things consist.
And he is the head of the body, the church: who is the beginning, the firstborn from the dead; that in all things he might have the preeminence.
For it pleased the Father that in him should all fullness dwell;
And, having made peace through the blood of his cross, by him to reconcile all things unto himself; by him, I say, whether they be things in earth, or things in heaven.
It is not uncommon for sermons and other Christian devotional/inspirational writings to cite this passage in comparison with some scientific concept: Just as gravity or atoms or molecules are the "glue" that holds the physical world together, so God or Jesus is the force that binds the spiritual world. The example involving laminin glycoprotein cited above is one example of this form, with the addition of a graphic meant to illustrate how God's design is evident (in the shape of a cross) in the molecular structure of laminin — what literally holds us together (in a biological sense) was clearly created by He who spiritually holds us together. This particular example is based on the work of Christian pastor/evangelist Louie Giglio, as seen in the following video clip:
Discussions about whether or not nature evinces signs of a purposeful (Christian) creator are theological/scientific debates that can (and do) fill volumes, so we'll just note a few items to consider:
- The structure of laminin antedates by many thousands of years traditional Christian accounts of the life of Jesus.
- A cross-like shape is a very simple structure that is commonly found in elements created naturally or accidentally.
- It is uncertain whether the form of the original crucifixion device was a stake, a T-shape, or the familiar cross of modern Christian iconography.
- One could find the shape of laminin to be reminiscent of a variety of common symbols aside from the cross. Some viewers say it reminds them more of a caduceus:
And when the illustration is returned to its original orientation, many liken it to the appearance of a sword:
- Perhaps most important, molecular diagrams like the one used here are generally intended to represent those structures in ways that make them easy for humans to conceptualize and work with, not to be exact reproductions of the molecules' actual visual appearances. One electron micrograph of EHS-laminin, for example, looks like this:
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