Tumor cell plasticity: the challenge to catch a moving target

Abstract

Every cancer cell is ''different''-within one and the same tumor, between different lesions originating from the same tumor, among different patients suffering from the same tumor type, and certainly between different tumor types. The complexity of tumor development, with its genetic, phenotypic and functional heterogeneity and plasticity within tumors and between primary tumors and metastases, underlies the unpredictable influences and stimuli of a tumor-associated inflammatory microenvironment, immune response, mechanical and metabolic stress, therapy-induced inflammation or interaction with microbiota. The stochastic and context dependent nature of these factors accounts for the difficulties to investigate the impact of resulting cell plasticity on tumor development, and justifies the challenge to prevent tumor recurrence. The emerging concept of cell plasticity and reciprocity (to change the phenotype by processing signals from the environment) throws more light on the actual complexity of tumor heterogeneity than can be expected solely from a unidirectional, classical cancer stem cell (CSC) model. To date, it remains widely unclear to what extent cell plasticity impacts tumor development, and it is difficult to assess by current methods. As a high tumor plasticity is likely to predict a poor outcome for patients, the future therapeutic challenge will be the development of personalized treatment strategies to predict and finally prevent cell plasticity in patients.

Immunotargeting of Antigen xCT Attenuates Stem-like Cell Behavior and Metastatic Progression in Breast Cancer

“…However, the identification of ideal CSC-associated targets is a particularly tough task because CSC appear to be "moving targets" that switch between different cell states during cancer progression (30). Hence, antigens that are upregulated in CSC but also present in more differentiated cancer cells would appear to be outstanding candidates.…”

Genetics and metabolic deregulation following cancer initiation: A world to explore

“…This process is characterized by genetic repression of epithelial cadherin (E-cadherin) promoter, followed by the neural cadherin (N-cadherin) gene expression, reducing the intercellular adhesion [11,35,44,61]. For these reasons, the E-to Ncadherin genetic switching is another important EMT hallmark, being observed in the first steps of carcinogenesis [35,42,45,47,49,62].…”

“…Metastasis is the last and worst consequence of cancer, being responsible by more than 90% of all death associated with solid tumors in both humans and animals [11,61]. Metastasis is the result of multiple steps, characterized by basal membrane and ECM degradation, local invasion and transformed cell migration for distant sites [49].…”

“…Epithelial cell plasticity is a metazoan conserved characteristic [11]. Epithelial cells are characterized by apical-basal polarity and a strong intercellular adhesion [42,43].…”

“…These models are based on tumor microenvironment understanding [10,11]. According to these models, cancer emerges from: (1) a pathogenic stimulus, induced by physical, chemical or biological agent and (2) a chronic and subclinical inflammation accompanied by (3) fibrotic process [1].…”