Dissecting the Emerging Role of Cancer-associated Adipocyte-derived Cytokines in Remodeling Breast Cancer Progression

Breast cancer has been reported to transcend lung cancer as the most commonly diagnosed cancer in women all over the world. Adipocytes, serving as energy storage and endocrine cells, are the major stromal cells in the breast. Cancer-associated adipocytes (CAAs) are adjacent and dedifferentiated adipocytes located at the invasive front of human breast tumors. Adipocytes can transform into CAA phenotype with morphological and biological changes under the remodeling of breast cancer cells. CAAs play an essential role in breast cancer progression, including remodeling the tumor microenvironment (TME), regulating immunity, and interacting with breast cancer cells. CAAs possess peculiar secretomes and are accordingly capable to promote proliferation, invasiveness, angiogenesis, metastasis, immune escape, and drug resistance of breast cancer cells. There is a complex and coordinated crosstalk among CAAs, immune cells, and breast cancer cells. CAAs can release a variety of cytokines, including IL-6, IL-8, IL-1β, CCL5, CCL2, VEGF, G-CSF, IGF-1, and IGFBP, thereby promoting immune cell recruitment and macrophage polarization, and ultimately stimulating malignant behaviors in breast cancer cells. Here, we aim to provide a comprehensive description of CAA-derived cytokines, including their impact on cancer cell behaviors, immune regulation, breast cancer diagnosis, and treatment. A deeper understanding of CAA performance and interactions with specific TME cell populations will provide better strategies for cancer treatment and breast reconstruction after mastectomy.