Multi-Faceted Role of Cancer-Associated Adipocytes in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer, especially in obese patients, and the second cause of cancer-related death worldwide. Based on these data, extensive research has been performed over the last decades to decipher the pivotal role of the tumor microenvironment (TME) and its cellular and molecular components in CRC development and progression. In this regard, substantial progress has been made in the identification of cancer-associated adipocytes’ (CAAs) characteristics, considering their active role in the CCR tumor niche, by releasing a panel of metabolites, growth factors, and inflammatory adipokines, which assist the cancer cells’ development. Disposed in the tumor invasion front, CAAs exhibit a fibroblastic-like phenotype and establish a bidirectional molecular dialogue with colorectal tumor cells, which leads to functional changes in both cell types and contributes to tumor progression. CAAs also modulate the antitumor immune cells’ response and promote metabolic reprogramming and chemotherapeutic resistance in colon cancer cells. This review aims to report recent cumulative data regarding the molecular mechanisms of CAAs’ differentiation and their activity spectrum in the TME of CRC. A better understanding of CAAs and the molecular interplay between CAAs and tumor cells will provide insights into tumor biology and may open the perspective of new therapeutic opportunities in CRC patients.

Prognostic Impact of Visceral Adipose Tissue Imaging Parameters in Patients with Cholangiocarcinoma after Surgical Resection

“…These dysfunctional adipocytes and infiltrated immune cells in the adipose tissue secrete diverse cytokines and adipokines that provoke a pro-inflammatory microenvironment and remodel the extracellular matrix, thereby providing a favorable microenvironment for cancer growth and metastasis [10,18,19]. Furthermore, studies have shown that adipocytes near the cancer-invasive front are transformed into small-sized cells showing fibroblast-like features, which then release pro-inflammatory cytokines and chemokines, increase glucose metabolism, and provide fatty acids to cancer cells as energy fuel [20,21]. These modified adipocytes are referred to as cancer-associated adipocytes, and they are now considered to have crucial impacts on cancer growth, metastasis, and angiogenesis [21].…”

“…Furthermore, studies have shown that adipocytes near the cancer-invasive front are transformed into small-sized cells showing fibroblast-like features, which then release pro-inflammatory cytokines and chemokines, increase glucose metabolism, and provide fatty acids to cancer cells as energy fuel [20,21]. These modified adipocytes are referred to as cancer-associated adipocytes, and they are now considered to have crucial impacts on cancer growth, metastasis, and angiogenesis [21].…”

Ginsenosides: an immunomodulator for the treatment of colorectal cancer

“…CAAs promote metabolic reprogramming and chemoresistance in colon cancer cells. CAAs release adipokines and metabolic factors to regulate the immune response of anti-tumor immune cells ( Harmon et al, 2019 ; Grigoras and Amalinei, 2023 ). CAAs contribute to the formation of a low-grade chronic inflammatory environment conducive to tumorigenesis, the mechanism being that CAAs influence the TME by releasing pro-inflammatory factors IL-1β, IL-6, IL-8, and TNF-α ( Grigoras and Amalinei, 2023 ).…”

“…CAAs release adipokines and metabolic factors to regulate the immune response of anti-tumor immune cells ( Harmon et al, 2019 ; Grigoras and Amalinei, 2023 ). CAAs contribute to the formation of a low-grade chronic inflammatory environment conducive to tumorigenesis, the mechanism being that CAAs influence the TME by releasing pro-inflammatory factors IL-1β, IL-6, IL-8, and TNF-α ( Grigoras and Amalinei, 2023 ). In addition, CAAs are frequently located at the front of invasive colorectal cancer, exhibiting a fibroblast-like phenotype, and establish a bidirectional molecular dialogue with colorectal tumor cells, leading to functional changes in normal cells and promoting CRC invasion ( Munteanu et al, 2020 ).…”