The evolving tumor-associated adipose tissue microenvironment in breast cancer: from cancer initiation to metastatic outgrowth.

Abstract

Adipocytes represent a significant proportion of breast tissue, comprising between 3.7 and 37% of stromal tissue. They play a pivotal role in metabolic regulation, energy supply, metabolic regulation, support effects, and cytokine release within the breast. In breast cancer (BC) tissue, adipocytes engage in intricate crosstalk with BC cells, playing a key role in tumor proliferation, invasion, metastasis formation, and metabolic remodeling. This is due to the provision of hormones, adipokines, and fatty acids to tumor cells by the adipocytes. With the initiation of metastatic outgrowth of BC, the peritumoral adipose tissue exhibits abundant and intricate changes based on its original construction and function, which convert it into a tumor-associated adipose tissue microenvironment (TAAME). It includes some specific adipocytes: adipose-derived stem cells (ASCs), cancer-associated adipocytes (CAAs), adipocyte-derived fibroblasts (ADFs), etc. From a mechanistic standpoint, specific adipocytes can facilitate the proliferation, invasion, metastasis, and angiogenesis of BC cells by secreting a multitude of cytokines (IL-6) and adipokines (leptin), which collectively create an environment conducive to BC progression. It is of paramount importance to recognize the TAAME as a crucial target for the diagnosis, treatment, and drug resistance of BC. Consequently, the review presents an overview of the characteristics and interactions of specific adipocytes within TAAME cell populations. This will facilitate the development of more effective personalized therapies against BC progression, relapse, and metastasis.