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  • Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop.

Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop.

BMC cancer (2013-03-28)
Daniel Öhlund, Oskar Franklin, Erik Lundberg, Christina Lundin, Malin Sund
ABSTRACT

Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized. The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule. We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis. We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Collagen Type IV Antibody, Chemicon®, from goat
Sigma-Aldrich
Anti-Integrin β1 Antibody, clone P5D2, clone P5D2, Chemicon®, from mouse
Sigma-Aldrich
Anti-Integrin α1 Antibody, clone FB12, clone FB12, Chemicon®, from mouse
Sigma-Aldrich
Anti-Integrin α2 Antibody, clone P1E6, clone P1E6, Chemicon®, from mouse
Sigma-Aldrich
Anti-Collagen Type IV α 2 Chain Antibody, clone 23IIC3, ascites fluid, clone 23IIC3, Chemicon®
Sigma-Aldrich
Anti-Laminin gamma 1 Antibody, clone A5, clone A5, Chemicon®, from rat