The progression of a
tumor from benign and localized to invasive and metastatic growth is the major cause of poor clinical outcome in
cancer patients. Much like in a healing wound, the deposition of
fibrin(
ogen), along with other adhesive
glycoproteins, into the extracellular matrix (ECM) serves as a scaffold to support binding of
growth factors and to promote the cellular responses of adhesion, proliferation, and migration during angiogenesis and
tumor cell growth. Inappropriate synthesis and deposition of ECM constituents is linked to altered regulation of cell proliferation, leading to
tumor cell growth and malignant transformation.
Fibrin deposition occurs within the stroma of a majority of
tumor types. In contrast, abundant FBG, not
fibrin, is present within the stroma of breast
cancers. It is thought to originate from exudation of plasma FBG and subsequent deposition into the
tumor stroma and not endogenous synthesis and secretion of FBG by
breast tumor cells. However, we show that MCF-7 human
breast cancer cells synthesize and secrete FBG
polypeptides, suggesting that the origin of FBG in the stroma of
breast carcinoma may be due to endogenous synthesis and deposition. Moreover, FBG assembles into ECM as conformationally altered FBG, not as
fibrin. Studies in our laboratory demonstrate that FBG alters the ability of
breast cancer cells to migrate. Together, the results of studies from our laboratory, as well as the laboratories of others, indicate that the presence of
fibrin(
ogen) within the
tumor stroma likely affects the progression of
tumor cell growth and
metastasis. This review focuses on FBG within
tumors and its relationship with other
tumor constituents, ultimately focusing on the role of FBG in
breast cancer.