Decorin Gene Therapy for Cancer

Cancer-associated fibroblasts (CAFs), which are the most abundant and active cells within the tumor microenvironment (TME), promote tumor progression, angiogenesis, and metastasis through the secretion of high levels of several pro-carcinogenic cytokines. TME also includes extracellular matrix (ECM), an acellular structure with a variety of components that are essential to maintain tissue homeostasis. During carcinogenesis, ECM proteins assist tumor onset and progression.

Decorin (DCN), an extracellular matrix protein expressed in both stromal and epithelial cells, is involved in controlling tumorigenesis and has been proposed as “a guardian from the matrix”. Indeed, DCN was indetectable within the tumor parenchyma of several cancer types, and a reduction in DCN levels was linked to poor prognosis.

We have recently shown that DCN downregulation activates breast stromal fibroblasts and promotes their pro-carcinogenic effects through the IL-6/STAT3 signaling pathway. Therefore, our major aim is to investigate the possible use of human recombinant DCN (rhDCN) as a gene therapeutic agent for cancer. We are testing the anti-cancer effects of rhDCN on various types of cancer cells, on active CAFs, and on angiogenesis both in vitro and in adequate animal models. The obtained results will lead to the identification of a natural anti-cancer protein that can be utilized for gene therapy to target both cancer cells and their supporting fibroblasts.

This therapeutic approach is expected to be efficient with fewer side effects.