Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis

Abstract

Cancer divergence has many facets other than being considered a genetic term. It is a tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates the opportunity to explore the possible mechanism in the surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their tumor microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, and fibroblast cells. Cancer stem cells (CSCs) or cancer stem-like cells are a small sub-set of the population within cancer cells believed to be a responsible player in the self-renewal, metastasis, and therapy response of cancer cells. The correlation between TME and CSCs remains an enigma in understanding the events of metastasis and therapy resistance in cancer biology. Recent evidence suggests that TME dictates the CSCs maintenance to arbitrate cancer progression and metastasis. The immune, inflammatory, endothelial, adipocyte, and fibroblast cells in the TME release growth factors, cytokines, chemokines, microRNAs, and exosomes that provide cues for the gain and maintenance of CSC features. These intricate cross-talks are fueled to evolve into aggressive, invasive, migratory phenotypes for cancer development. In this review, we have abridged the recent developments in the role of the TME factors in CSC maintenance and how these events influence the transition of tumor progression to further translate into metastasis and therapy resistance in cancer.

G‐protein‐coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1‐mediated redox modulation

“…50 More and more epidemiologic and research evidence supports an association of obesity with breast, gastric, and colon cancer and so on. 8,[51][52][53] Adipose tissue is the second most important site of estrogen production, it remains unclear whether estrogen derived from adipose tissue promotes peritoneal metastasis of gastric cancer, the mechanism of tendency toward peritoneal metastasis in GC is still not clear.…”

“…Traditionally described as an inert storage site for lipids, adipose tissue is now recognized as a real organ with both metabolic and endocrine functions that secrete cytokines and hormones 50 . More and more epidemiologic and research evidence supports an association of obesity with breast, gastric, and colon cancer and so on 8,51–53 . Adipose tissue is the second most important site of estrogen production, it remains unclear whether estrogen derived from adipose tissue promotes peritoneal metastasis of gastric cancer, the mechanism of tendency toward peritoneal metastasis in GC is still not clear.…”

Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells

“…CSCs play an influential role in tumor progression, recurrence, and chemoresistance due to their typical stemness characteristics. The TME components of CAFs, TAMs, MSCs, and noncellular factors have been reported to promote tumor cell stemness via bidirectional cross talks between tumor cells and secreted factors 282 . For example, CAFs could promote tumor stemness through the FGF4–FGF2 axis and high‐mobility group box 1 283,284 .…”

Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

“…Tumor microenvironment (TME) is a unique environment and composed of many other types of cells, such as stromal, endothelial and immune cells, which has shown to participate in tumor development, initiation and progression as well as metastasis ( Eulberg et al, 2022 ; Nallasamy et al, 2022 ). The TME cellular components consist of MDSCs, Treg cells, M1 macrophages, M2 macrophages, cytotoxic CD8 + T cells and NK cells ( Gajewski et al, 2013 ; Cao et al, 2022 ).…”