ALSO - Dean Steelant is providing pizza (cheese and pepperoni) as well as drinks for those attending the Seminar. When you see our STEM Dean, give him a HUGE "Thank You!"
Tuesday, September 20, 2016
Special Seminar Speaker - September 23rd: BE THERE!
This coming Friday, we have a very special guest speaker, Dr. Severine Van Slambrouck. She is most willing to meet students and faculty while she is here. Therefore, if you care to chat with her, please let me know ASAP. [No background reading was suggested for this seminar.]
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Dr. Severine Van Slambrouck covered prostate cancer research. More specifically, she focused on the mechanisms of cancer cell invasion that has implications for identifying new target therapies. She uses the LNCaP prostate cancer progression cell model system and compares the LNCaP primary tumor cells to the C4-2B cells, which are derived from metastatic sites. She specifically focuses on their adhesion and invasion into collagen 1 and found that C4-2B cells interact, invade, and degrade the matrix of collagen 1 more than LNCaP cells do. I am not much of a biochemist so for my question, I was wondering how you could apply Dr. Van Slambrouck’s findings of C4-2B cell interactions with collagen 1 to drug discovery and therapies used to treat/prevent cancer?
ReplyDeleteDr. Van Slambrouck’s research centered around the observation that a tumor’s potential for metastasis depends on its ability to interact, invade, and eventually degrade the collagen 1 in its extracellular environment. This vital, yet fatal interaction is mediated by the specificity of the Integrin alpha2 beta1 receptor on the tumor cells for collagen 1. Since this receptor’s specificity is seemingly dependent on the density of sialic acids attached to the glycosylated alpha2 beta1 receptor, I would propose a treatment that prevents sialic acid from being added to the receptor. Sialic acid residues are linked by sialyltransferases, so developing a drug that inhibits this enzyme could prove a successful prevention of tumor metastasis.
DeleteThe lecture itself was extremely interesting, though a lot of it was way above my area of knowledge on the topic. But I think that by studying C4-2B interactions with collagen 1, it becomes possible to have a better understanding of how the metastatic cells grow and migrate. If we are able to gain a more comprehensive understanding of how these cells behave, it becomes easier to create medical procedures or medications that could possibly target or block specific metastatic cells from growing or spreading.
ReplyDeleteYes, the lecture was certainly interesting, but it was hard for me to understand as well because it isn't my area of expertise.
DeleteThis may be way off the mark, but I believe that the reason for which Dr. Van Slambrouck developed the C4-2B cell line was to compare differences between metastasized cells and their parent tumor cells (in this case LNCaP cells). It appears that the ability for malignant tumor cells to invade and degrade ECM is facilitated by a change in the structure of integrin α1β1. Specifically, the addition of sialic acid residues to the extracellular head of α1β1 permits integrin-ligand binding with collagen I, a major component of ECM. In non-tumorigenic cells integrin proteins regulate cell migration, proliferation, survival, and apoptosis. These faculties are critical to the survival of an organism, so we simply can’t eliminate all α1β1 proteins from the cell membrane in hopes of stopping metastasis. However, the work of Dr. Van Slambrouck could be used to design drugs that maintain normal function of integrin α1β1 by preventing sialylation. This could be accomplished by targeting benign tumor cells and introducing a molecule that binds to sialic acid and thereby prevents its interaction with the α1β1 protein.
ReplyDeleteThat's an interesting idea! I didn't even think of it that way, great perspective.
DeleteThe presentation was more informative especially more interested on sialylation and glycosylation. The tumor cells showed to exhibit changes in cell surface glycosylation as a results of dysregulated glycosyltransferases and glycosidases. An increase in the expression of certain sialylated glycans exhibit prominent feature of many transformed cells. Altered sialylation has been majorly related with metastatic cell behaviors including invasion in collagen I and enhanced cell survival. Moreover, there is need for further information regarding the molecular details of how efficient sialylated structures or sialylated carrier proteins regulate cell signaling to control responses such as adhesion to collagen I, cell matrix interaction, cell-cell aggregation and migration or resistance to specific apoptotic pathways.
ReplyDeleteDr. Severine Van Slambrouck looked at how the integrin receptors on collagen 1 in vitro are altered when sialic acid is present and binds to them. This change in the receptors allows the C4-2B cells to bind onto the collagen, causing interaction and invasion and, ultimately, metastatic tumor formation. I think one could look at what other potential residues could possibly prevent C4-2B cells, or any other cell or protein that causes tumor formation, from binding to the collagen structure. One could also apply this to cancers other than prostate, and discover newer, more efficient treatments by learning what other structures/proteins can help prevent invasion of cells such as C4-2B cells.
ReplyDeleteDr. Severine Van Slambrouck’s research discussed a reorganization of AsialoGM1 with α2β1. This enhanced interaction lead to an ultimate increase in MMPs which would act to degrade ECM and allow escape from the primary site and enhanced metastasis. A possible solution to this problem could the use of bivalent antibodies. If veritable regions could be raised against both AsialoGM1 and α2β1 then the antibody should have strong binding to C4-2B cells. Hopefully, the blocking of these receptors would prevent or at least slow metastasis without much interference to healthy cells. Also, if the antibody was human or humanized, NK cells might be able to perform antibody-dependent cell-mediated cytotoxicity (ADCC) and destroy some of the cancer cells. However, this idea would require much more research and genetic profiling of surrounding cells.
ReplyDeleteAs someone who studies immunology, I like the idea of using antibodies as a possible way to prevent migration of the metastasized cells.
DeleteI found Dr. Van Slambrouck's presentation to be very interesting, although I was not completely familiar with a few of the topics she discussed. I think that by further studying the interactions between sialic acid and the integrin receptors on collagen 1, as well as C4-2B interactions with collagen 1, it is easier to understand the metastatic processes of cancer cells. This would, of course, make it easier to find treatment methods.
ReplyDeleteHigh mortality rates caused by cancer are attributed to the mestatic spread of cancer cells to vital organs, prostrate cancer is not an exception where its mestatic to the bone is the main cause of death.Dr. Serevine Van Slambrouck presentation was really appealing and educative.Glycosylation allows malignant cells to promote cell mobility, cell adhesion, and even receptors activation thus attributing to the invasive phenotype.Therefore by studying the C4-2B cell interactions with collagen 1 will provide a deeper understanding of the biological and biochemical mechanisms of cancer metastatis hence leading to more effective therapies for the prostate cancer patient.
ReplyDeleteDrug targeting could be founded on the quality of C4-2B cells having colocalized expression of integrin alpha 2 beta 2 receptors and asialoGM1, providing possible increased binding affinity relative to other expressing cells. Inhibition of these integrin receptors might decelerate tumor progression/metastasis by suppressing adhesion/invasion into the extracellular matrix.
ReplyDeleteDr. Van Slambrouck’s talk on metastatic prostate cancer provided an example of one of the many instances in which disciplines (biology, chemistry, biochemistry, and medicine) cross to solve a common goal. It was mentioned that the integrin α2β2 receptors mediate the adhesion as well as the invasion of metastatic C42B cells to collagen I, allowing for migration of the cancer. It is a possibility that maybe these receptors could be blocked via drug adhesion in order to prevent metastasis. This then would localize the cancer to the prostate and allow for known means of treatment, such as brachytherapy, to ensue.
ReplyDeleteMetastasis of tumor cells are of crucial importance in prostate cancer. Dr. Severine used LNCaP primary tumor cells and compare it to C4-2B cells which are derived for bone metastatic sites. It was noticed that C4-2B cells migrate faster than parental LNCaP. The integrin a2b1 and asialoGM1 were important in cell migration and suppression of these two receptors with antibodies proved their role in cell migration in lab. The integrin a2b1 and asialoGM1 receptors work with C4-2B cell to mediate alternation in adhesion, migration and invasiveness. But the problem remains that it would not be possible to block all a2b1 and asialoGM1 receptors in the body to prevent metastasis of prostate cancer. She also mentioned Neuroaminidase (NEU3) which is a sialidase is often detected in pathological exams of prostate cancer. Sialidases remove sialic acid from sialylated gangliosidases. If there is a possibility to block the expression of sialidases, along with the localized blockage of asialoGM1 and integrin a1b2 receptors, the metastasis of prostate cancer can be halted.
ReplyDeleteI wonder if the triggering event is through mutations or via cell signaling. I imagine it is a cell signaling event that changes the cells to the metastatic version similar to the events that happen in microbial colonies.
ReplyDeleteDr. Van Slambrouk looked at the mechanism of cancer cell-cell aggregation at a primary tumor site, cell-matrix interaction, migration, and invasion through aberrant glycolysis and membrane disorganization in metastatic prostate cancer. She studied the question of why do cancer cells spread to try to identify new targets for therapy and diagnosis. Primary tumor site leads to interaction with matrix where cells begin to release proteases invading tissue and entering the blood stream resulting in spreading. Survival rates of patients decrease with metastasis of cancer; therefore, it is important to study the mechanism of this action in order to find effective treatments. Very interesting presentation from both biological and chemical aspects.
ReplyDelete