Cell competition, cooperation, and cancer

Abstract

Complex multicellular organisms require quantitative and qualitative assessments on each of their constitutive cell types to ensure coordinated and cooperative behavior towards overall functional proficiency. Cell competition represents one of the operating arms of such quality control mechanisms and relies on fitness comparison among individual cells. However, what is exactly included in the fitness equation for each cell type is still uncertain. Evidence will be discussed to suggest that the ability of the cell to integrate and collaborate within the organismal community represents an integral part of the best fitness phenotype. Thus, under normal conditions, cell competition will select against the emergence of altered cells with disruptive behavior towards tissue integrity and/or tissue pattern formation. On the other hand, the winner phenotype prevailing as a result of cell competition does not entail, by itself, any degree of growth autonomy. While cell competition per se should not be considered as a biological driving force towards the emergence of the neoplastic phenotype, it is possible that the molecular machinery involved in the winner/loser interaction could be hijacked by evolving cancer cell populations.

The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease

“…Another risk factor that cells can sense is loss of architectural integrity. Mutations that lead to the loss of cell polarity and tissue patterning can reduce function and trigger cancer initiation [125,140]. Such phenotypes are normally considered losers, and the selective elimination of these cells by neighboring wild-type counterparts has been described [140].…”

“…Tissue integrity is also guaranteed by direct cell competition between homotypic cells [125] (Fig. 3).…”

The Field of Cell Competition Comes of Age: Semantics and Technological Synergy

“…One key difference between these two patterns of cellular competition is the nature of the tissue it occurs within—where one clone may come to outcompete its neighbours in an epithelial layer, spatially separated crypts isolate clones, limiting their spread. While perhaps seeming straightforward, the dynamics of clonal competition and neoplastic growth are increasingly complex, and have been recently well reviewed elsewhere ( Marongiu et al, 2021 ).…”

Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice

“…49 Cellular senescence also plays roles in the tissue microenvironment, contributing to the neoplastic-prone tissue landscape of old age. 50 Elevated levels of SASPs can recruit immune cells to promote cell senescence via cell cycle arrest during wound healing, tissue remodeling, and tumor development. 51 However, unexpected accumulation of senescent cells with aging can be detrimental to tissue homeostasis and impairs tissue regeneration, facilitating tumorigenesis.…”

“…Cellular senescence has a capability of modulating the cellular microenvironment to maintain local homeostasis 49 . Cellular senescence also plays roles in the tissue microenvironment, contributing to the neoplastic‐prone tissue landscape of old age 50 . Elevated levels of SASPs can recruit immune cells to promote cell senescence via cell cycle arrest during wound healing, tissue remodeling, and tumor development 51 .…”