Role of tissue microenvironment resident adipocytes in colon cancer

Abstract

Colorectal cancer (CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment (TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors (angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to cross-talk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.

Adipose Tissue and Its Role in Microenvironment of the Colorectal Adenocarcinoma Cancer Cell

“…Redox molecules are capable of inducing lipolysis in adenocarcinoma cells that results in glycerol production, which can be incorporated into the glycolytic metabolic pathway [14]. Such pathological changes in normal metabolism c a n a c t i v a t e m o re ra p i d g row t h a n d subsequently much significant malignant metastatic tumor phenotype, including RC [15]. Such changes are accompanied by changes in the microenvironment of healthy cells, infiltration of tumor-associated immune cells that trigger the process of chronic inflammation and enhance oxidative stress.…”

Role of adipose tissue in the development and progression of colorectal cancer

“…По одной из версий сигналы от опухолевого микроокружения запускают унаследованные генетические изменения в раковых клетках, ответственных за прогрессию опухоли [31]. Индуцирует ли жировая ткань прогрессию только некоторых молекулярных вариантов КРР, или окружающие опухоль адипоциты инактивируют гены-супрессоры и/или активируют онкогены, до сих пор остается неясным [10].…”

“…При взаимодействии с клетками опухоли адипоциты дедифференцируются в преадипоциты или даже репрограммируются в опухольассоциированные адипоциты [6]: адипоциты, находящиеся в непосредственной близости от опухолевого инвазивного фронта, приобретают фибробластоподобный фенотип. Резидентные адипоциты опухолей также изменяют свою морфологию и функции, становясь меньше по размеру (за счет активации липолитической активности), у них уменьшается количество маркеров, характерных для жировых клеток (адипонектин, резистин, белок, связывающий жирные кислоты 4, белок адипоцитов-2) [9], но повышается секреция провоспалительных цитокинов (интерлейкины (IL) 6, 8, 1β, фактор некроза опухоли-альфа -TNF-α), митогенных (IGF-1) и ангиогенных факторов (VEGF) и MCP-1 [10,11].…”

Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled

“…Aside from functioning as energy (lipid) storage, it produces adipokines, metabolic substrates, growth factors, hormones, and immune mediators, and it contains other stromal components, such as fibroblasts, stromal vascular fraction, macrophages and other immune cells, nerve tissue, and extracellular matrix [ 133 ]. In presence of malignant setting, normal adipocytes rapidly acquire a highly active phenotype (CAAs) and respond by metabolic and secretory profile changes, causing pro-inflammatory, pro-invasive, proliferative, and radio- and chemoresistance effect on cancer cells [ 28 , 134 , 135 , 136 , 137 , 138 , 139 ].…”