Caveolin-1 and Cancer-Associated Stromal Fibroblasts

For several years, breast cancer has been strictly studied with a focus on the epithelial cancer cells that constitute the tumor mass. As a result, inherited or acquired mutations of important tumor suppressors, such as p53 and BRCA1 (breast cancer 1), were discovered in epithelial cells and shown to predispose patients to the development of breast cancer [1]. However, only a small percentage of breast cancer cases can be explained by the presence of epithelial mutations. As such, changes in protein expression of several other markers have also been linked to breast cancer prognosis, such as HER2 (human epidermal growth factor receptor 2), estrogen receptor (ER), progesterone receptor (PR), Bcl2 (B-cell lymphoma 2), and survivin, which are currently used for early diagnosis and therapeutic stratification [2, 3]. Despite the important contribution of epithelial cells to tumor initiation and progression, recent reports have shown that they function as part of a complex multifaceted entity with their adjacent neighboring stromal cells, the stroma. Indeed, several new lines of evidence demonstrate an important dynamic role for the tumor microenvironment in tumor initiation, progression, angiogenesis, and chemo-resistance, through the action of cancer-associated fibroblasts (CAFs), a major cell type found in the cancer stroma [4]. The current chapter focuses on the role of CAFs in cancer initiation, progression, angiogenesis, and resistance to chemotherapy, with a focus on Caveolin-1 (Cav-1), an important structural protein of caveolae that has recently been shown to be play and important functional role in the tumor stroma.