Cellular reprogramming in skin cancer

Abstract

Early primitive stem cells have long been viewed as the cancer cells of origin (tumor initiating target cells) due to their intrinsic features of self-renewal and longevity. However, emerging evidence suggests a surprising capacity for normal committed cells to function as reserve stem cells upon reprogramming as a consequence of tissue damage resulting in inflammation and wound healing. This results in an alternative concept positing that tumors may originate from differentiated cells that can re-acquire stem cell properties due to genetic or epigenetic reprogramming. It is likely that both models are correct, and that a continuum of potential cells of origin exists, ranging from early primitive stem cells to committed progenitor or even terminally differentiated cells. A combination of the nature of the target cell and the specific types of gene mutations introduced determine tumor cell lineage, as well as potential for malignant conversion. Evidence from mouse skin models of carcinogenesis suggests that initiated cells at different stages within a stem cell hierarchy have varying degrees of requirement for reprogramming (e.g. inflammation stimuli), depending on their degree of differentiation. This article will present evidence in favor of these concepts that has been developed from studies of several mouse models of skin carcinogenesis.

The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing

“…One of the core questions in cancer biology relates to the identity and nature of the cancer cell of origin leading to tumor initiation [ 29 ]. Evidence from mouse skin models of carcinogenesis suggests that initiated cells at different stages within a stem cell hierarchy require varying degrees of reprogramming depending on their degree of differentiation [ 30 ]. For tumorigenesis, various interrelated determinants govern this complex tumor-host interaction, including GJIC, which plays a central role in coordinating intercellular signal-transduction pathways to control tissue homeostasis [ 31 ].…”

Refining the role for adult stem cells as cancer cells of origin

“…This significantly enhanced downstream Wnt signaling, causing robust dedifferentiation of terminally differentiated villus cells expressing markers of stem cells, which were able to generate intestinal adenomas[132]. This study suggests inflammation could alter the CCOs by inducing cell identity changes and imparting stem cell characteristics on TACs or differentiated cells [132,134]. To support this finding, mice treated with infectious bacteria showed prostatic inflammation, which resulted in the differentiation of basal cells towards the luminal lineage [135].…”

Cancer Microenvironment: What Can We Learn from the Stem Cell Niche

“…ESCs can represent the element from which the cancer is originated [ 61 ]. Microenvironment of chronic inflammation can be also responsible for malignant reprogramming of ESC [ 62 ]. This process seems to be more frequently occurring in bulge keratin K15/K19-positive cells than in interfollicular basal keratin K5/K14-positive cells and interfollicular suprabasal keratin K1/K10 and involucrin-positive cells [ 63 ].…”

“…When RAS/MAPK pathway is deregulated in mouse epidermis, squamous cell carcinoma can be expected in mouse model. In the case of PTCH/Shh signaling disturbance, development of basal cell carcinoma is likely in both mouse and human [ 62 , 63 , 64 , 65 , 66 ]. In context of cancer formation, increasing number of mitotic divisions of stem cells in different tissues reflects increased risk of cancer formation [ 67 ].…”