Mechanism of Extracellular Matrix Induced Tumor Survival and Drug Resistance in Castration-Resistant Prostate Cancer

Abstract

Extra-cellular matrix (ECM) is the three-dimensional environment in which cells thrive by influencing cell growth and survival through various signaling pathways aided by its molecular components in the ECM like water, minerals, proteoglycans, fibronectin, laminin and collagen. Due to its extensive impact on cellular activities, the ECM can play an integral role in imparting resistance to cancer drugs in tumors. Prostate cancer maturation is highly androgen-dependent and thus, the standard effective treatment in the case of prostate cancer is Androgen Deprivation Therapy (ADT). However, after a few years of androgen deprivation, the cancer progresses to Castration-Resistant Prostate Cancer (CRPC), which is the prevalence and growth of prostate cancer in the absence of androgen. Another therapy used for the treatment of prostate cancer is the use of PI3K inhibitor drugs, but CRPC exhibits resistance to the PI3K inhibitors. Also, >80% of CRPC metastasize to bone and the mechanism behind this phenomenon is yet not well understood. Bones are a rich source of collagen and hence, collagen can be one of the key components of the ECM that supports the niche formation and survival of prostate cancer during bone metastasis. The mechanism which imparts drug resistance to PI3K inhibition in CRPC is widely investigated. This study focusses on exploring the less known role of collagen in relaying resistance to PI3K inhibitors in C4-2 cells (CRPC cells), the understanding of which is crucial for the development of an effective treatment for CRPC.