Peking University - Juntendo University Joint Symposium on Cancer Research and Treatment

Tumor- and Metastasis-Promoting Roles of Carcinoma-Associated Fibroblasts in Human Breast Carcinomas

Abstract

The recent advance of precision medicine based on genetic information about a person’s disease would help us develop appropriate cancer diagnosis and treatment. However, the emergence of metastases and treatment failure, that accounts for cancer-related mortality in most cancer patients, is often conferred by tumor microenvironment presumably in a non-genetic fashion. Various non-neoplastic stromal cells orchestrating tumor microenvironment enable incipient carcinoma cells to acquire malignant phenotypes including invasion and metastatic traits and therapy-resistant propensity during the course of tumor progression.

Human carcinomas are not only composed of tumor cells but also comprised of non-neoplastic stroma cells, such as endothelial cells, leukocytes, macrophages, myofibroblasts, bone marrow-derived progenitors and abundant extracellular matrix (ECM). Fibroblast populations in tumor are termed carcinoma-associated fibroblasts (CAFs) that constitute a substantial proportion of the non-neoplastic mesenchymal cell compartment in various human tumors. To support the growth and progression of carcinoma cells, these fibroblasts are phenotypically converted from their progenitors to activated fibroblasts via interactions with nearby cancer cells during tumor progression. CAFs influence the hallmarks of carcinoma to promote tumor malignancy through the secretion of tumor-promoting growth factors, cytokines and exosomes, as well as through remodeling of the extracellular matrix. Recent studies have revealed the molecular mechanisms underlying CAF functions, especially in tumor invasion, metastasis and drug resistance. In this symposium, I introduce the impacts of recently identified biological roles of tumor- and metastasis-promoting CAFs for future therapeutic applications.