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Kenneth van Golen, PhD
KennethVanGolenPhD (Researcher (Verified) )| Communities: Breast Cancer | Answers: 8 |
| Member Since: Jun. 2012 |
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Professional Statement
Dr. van Golen is Associate Professor in the Department of Biological Sciences at University of Delaware.
The main interest of my laboratory is to understand the biology of Inflammatory breast cancer (IBC). IBC is an extremely aggressive form of breast cancer that is phenotypically unique form of breast cancer. IBC is hallmarked by distinct changes in the skin changes that resemble an infection or mastitis. IBC affects younger women (typically in thier late 20's or early 30's) and progresses rapidly. The rapid progression of the disease is thought to occur because of the propensity of the tumor cells to invade and reside in the dermal lymphatic vessels of the skin overlying the breast.
In 1999 our laboratory found that RhoC GTPase, one member of the Rho family, was overexpressed in inflammatory breast cancer. Later, we found that RhoC over expression was a prognostic marker for metastasis in small breast tumors (<1 cm in size). Since then we have begun to look at how RhoC confers a metastatic phenotype to inflammatory breast cancer and how it interacts with other Rho GTPases. Our studies have expanded to include pancreatic cancer and prostate cancer bone metastasis.
The Rho GTPases comprise a group of 23 small GTP binding proteins that play a significant role in nearly every cellular process. One of the most characterized roles of the Rho proteins is their ability to reorganize the cell cytoskeleton. Signals from the extracellular environment, transduced through growth factor receptors and/or cell adhesion molecules leads to the coordinated activation of Rho proteins and reorganization of the cytoskeleton. In turn, this leads to changes in cells shape, polarity, migratory and invasiveness.
The potent ability of the Rho proteins to affect cell migration and invasion has many implications for the dissemination and spread of cancer and in normal processes such as development and immunity. RhoC GTPase is associated with metastatic spread and thus appears to be a metastatic switch. Interestingly, RhoC is 91% homologous on the protein level to RhoA GTPase, yet the two proteins have completely different functions in the cell. One of our goals is to understand what makes these two GTPases distinct from one another.
A complete understanding of how the Rho proteins, particularly RhoC, can influence progression of a cancer cell to become metastatic is key to the development of anti-metastatic therapies. Aside from IBC our laboratory also has interests in understanding the mechansims underlying prostate cancer skeletal metastasis.
The main interest of my laboratory is to understand the biology of Inflammatory breast cancer (IBC). IBC is an extremely aggressive form of breast cancer that is phenotypically unique form of breast cancer. IBC is hallmarked by distinct changes in the skin changes that resemble an infection or mastitis. IBC affects younger women (typically in thier late 20's or early 30's) and progresses rapidly. The rapid progression of the disease is thought to occur because of the propensity of the tumor cells to invade and reside in the dermal lymphatic vessels of the skin overlying the breast.
In 1999 our laboratory found that RhoC GTPase, one member of the Rho family, was overexpressed in inflammatory breast cancer. Later, we found that RhoC over expression was a prognostic marker for metastasis in small breast tumors (<1 cm in size). Since then we have begun to look at how RhoC confers a metastatic phenotype to inflammatory breast cancer and how it interacts with other Rho GTPases. Our studies have expanded to include pancreatic cancer and prostate cancer bone metastasis.
The Rho GTPases comprise a group of 23 small GTP binding proteins that play a significant role in nearly every cellular process. One of the most characterized roles of the Rho proteins is their ability to reorganize the cell cytoskeleton. Signals from the extracellular environment, transduced through growth factor receptors and/or cell adhesion molecules leads to the coordinated activation of Rho proteins and reorganization of the cytoskeleton. In turn, this leads to changes in cells shape, polarity, migratory and invasiveness.
The potent ability of the Rho proteins to affect cell migration and invasion has many implications for the dissemination and spread of cancer and in normal processes such as development and immunity. RhoC GTPase is associated with metastatic spread and thus appears to be a metastatic switch. Interestingly, RhoC is 91% homologous on the protein level to RhoA GTPase, yet the two proteins have completely different functions in the cell. One of our goals is to understand what makes these two GTPases distinct from one another.
A complete understanding of how the Rho proteins, particularly RhoC, can influence progression of a cancer cell to become metastatic is key to the development of anti-metastatic therapies. Aside from IBC our laboratory also has interests in understanding the mechansims underlying prostate cancer skeletal metastasis.
Professional Info
Credential: PhD
School / University: University of Texas, Health Science Center
Areas of expertise: Inflammatory Breast Cancer
Hospital or other affiliation: Delaware Biotechnology Institute
Webpage:
http://www.bio.udel.edu/user/509
City: Newark
State: DE
Zip: 19716-2590
KennethVanGolenPhD Activities
Inflammatory breast cancer cells rapidly invade the dermal lymphatic vessels. The tumor cells form emboli within the dermal lymphatics and are thought to rapidly spread throughout the body. When diagnosing IBC, skin punch biopsies are taken and analyzed for emboli within the lymphatic vessels.
New answer by KennethVanGolenPhD (Researcher (Verified)) in topic(s) Inflammatory Breast Cancer, Breast Cancer, Inflammatory Breast Cancer Diagnosis, Breast Tumor, Breast Cancer Pathology, Breast Tumor Location, Cancer Pathology, Inflammatory Breast Cancer Pathology, Tumor Pathology, Tumor Location
1
Answer |
10 months ago
Inflammatory breast cancer (IBC) is very different from other types of breast and should be thought of completely independently. Primary IBC tumors form as sheets or cords of tumor cells in the breast but they quickly invade into the dermal lymphatic vessels and form emboli. Because of these features IBC typically cannot be visualized by mammography.
New answer by KennethVanGolenPhD (Researcher (Verified)) in topic(s) Tumor, Breast Cancer Screening, Breast Tumor Detection, Inflammatory Breast Cancer Diagnosis, Breast Cancer Types, Tumor Pathology, Primary Tumor, Breast Cancer Tumor, Inflammatory Breast Cance Screening, Inflammatory Breast Cancer, Inflammatory Breast Cancer Research, Breast Tumor, Breast Cancer Pathology, Inflammatory Breast Cancer Pathology
1
Answer |
10 months ago
This is an interesting question that researchers have been trying to address for a couple of decades now. Essentially, the tumor cells need to be competent on a number of levels to become invasive and migratory. Basically, the cells need to be able to be able to separate from other cells, respond by changing shape, produce enzymes that degrade the matrix around it. There are many other attributes that a cell needs in order to be metastatic in the body.
New answer by KennethVanGolenPhD (Researcher (Verified))
1
Answer |
10 months ago
Quite simply stated, if we can figure out how to prevent RhoC activation we can stop metastases from occurring. This is particularly relevant for certain cancers such as breast, prostate and melanoma, which are caught early and have the potential for metastasis. One other potential clinical use is that RhoC and other molecules involved in the RhoC-driven metastasis can be used as prognostic markers.
New answer by KennethVanGolenPhD (Researcher (Verified))
1
Answer |
10 months ago
We find that these signals come from the microenvironment. Many of the growth factors that activate RhoC are found in the circulation, particularly in cancer patients. The tumor cells themselves also produce many of these factors as well. Further, upon arrive at certain metastatic sites the prevalence of certain extracellular matrices can also activate RhoC.
New answer by KennethVanGolenPhD (Researcher (Verified))
1
Answer |
10 months ago
We have found several signaling processes that activate RhoC in cells depending on tumor type. In prostate cancer cells, we find that both growth factor activation (specifically insulin-like growth factor 1) and binding to certain extracellular matrices such as type I collagen activate RhoC. In pancreatic cancer, we find that RhoC activation via growth factors is negatively regulated by other types of signaling molecules, such as the scaffolding molecule caveolin-1. In inflammatory breast cancer, we find that growth factors such a epidermal growth factor (EGF) activates RhoC. In this case we have also found a relationship with caveolin-1 as well, except in this case it is the inverse of what we find in pancreatic cancer; caveolin-1 is a positive regulator of RhoC activation.
New answer by KennethVanGolenPhD (Researcher (Verified))
1
Answer |
10 months ago
Our early work compared the role of RhoC GTPase with that of other highly similar GTPases, specifically RhoA and RhoB, in different cancer types and in expressing RhoC in normal mammary epithelial cells. We found that RhoC is required to drive migration and invasion of tumor cells. Further, expression of RhoC in normally mammary epithelial cells made those cells motile as well. Later experiments demonstrated that knockout or knockdown of RhoC led to prevention of invasion and metastasis of tumor cells.
New answer by KennethVanGolenPhD (Researcher (Verified))
1
Answer |
10 months ago
RhoC GTPase is normally found in cells that are motile, such as
immune cells that migrate to sites of infection. RhoC is typically not expressed in cells that cancers arise from (epithelium). In motile immune cells, RhoC drives reorganization of the actin cytoskeleton allowing those cells to move. Metastatic cancer cells gain RhoC expression and activation (abnormally), which drives the cells ability to invade and migrate similar to that of normal immune cells.
immune cells that migrate to sites of infection. RhoC is typically not expressed in cells that cancers arise from (epithelium). In motile immune cells, RhoC drives reorganization of the actin cytoskeleton allowing those cells to move. Metastatic cancer cells gain RhoC expression and activation (abnormally), which drives the cells ability to invade and migrate similar to that of normal immune cells.
New answer by KennethVanGolenPhD (Researcher (Verified))
1
Answer |
10 months ago
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