Cancer-Associated Fibroblasts and Their Putative Role in Potentiating the Initiation and Development of Epithelial Ovarian Cancer

Abstract

The progression of ovarian cancer, from cell transformation through invasion of normal tissue, relies on communication between tumor cells and their adjacent stromal microenvironment. Through a natural selection process, an autocrine-paracrine communication loop establishes reciprocal reinforcement of growth and migration signals. Thus, the cancer-activated stromal response is similar to an off-switch-defective form of the normal, universal response needed to survive insult or injury. It is becoming clearer within the cancer literature base that tumor stroma plays a bimodal role in cancer development: it impedes neoplastic growth in normal tissue while encouraging migration and tumor growth in a co-opted desmoplastic response during tumor progression. In this review, we discuss this reciprocal influence that ovarian cancer epithelial cells may have on ovarian stromal cell-reactive phenotype, stromal cell behavior, disrupted signaling networks, and tumor suppressor status in the stroma, within the context of cancer fibroblast studies from alternate cancer tissue settings. We focus on the exchange of secreted factors, in particular interleukin 1β and SDF-1α, between activated fibroblasts and cancer cells as a key area for future investigation and therapeutic development. A better understanding of the bidirectional reliance of early epithelial cancer cells on activated stromal cells could lead to the identification of novel diagnostic stromal markers and targets for therapy.