Multi‑faceted role of cancer‑associated adipocytes in the tumor microenvironment (Review)

Abstract

Adipocytes are a type of stromal cell found in numerous different tissues that serve an active role in the tumor microenvironment. Cancer‑associated adipocytes (CAAs) display a malignant phenotype and are found at the invasive tumor front, which mediates the crosstalk network between adipocytes (the precursor cells that will become cancer‑associated adipocytes in the future) and cancer cells. The present review covers the mechanisms of adipocytes in the development of cancer, including metabolic reprogramming, chemotherapy resistance and adipokine regulation. Furthermore, the potential mechanisms involved in the adipocyte‑cancer cell cycle in various types of cancer, including breast, ovarian, colon and rectal cancer, are discussed. Deciphering the complex network of CAA‑cancer cell crosstalk will provide insights into tumor biology and optimize therapeutic strategies.

Keywords: CAA; TME; adipokines; chemotherapy resistance; metabolic reprogramming.

Figure 1.

Complex relationships among tumors, adipocytes and CAAs. At the cancer invasion front, adipocytes undergo lipolysis and transform into CAAs. CAAs are involved in the progression and metastasis of tumor cells. CAAs can secrete a variety of adipokines, release free fatty acids and exosomes to cancer cells for metabolic reprogramming. Alternatively, after receiving signals from malignant cells, CAAs can produce various growth factors, adipokines and adipocytokines, which directly affect the growth and invasion of tumor cells. CAA, cancer-associated adipocyte; MSC, mesenchymal stem cell; miRNA, microRNA.

Figure 2.

Potential methods for targeting CAAs in the treatment of tumors. Potential therapeutic approaches include limiting adipocyte recruitment, targeting the activation of CAAS, reprogramming CAAs to CAA precursors and targeting CAAs in combination with standard therapies. CAA, cancer-associated adipocyte.