Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations

Abstract

A tumor originates from a normal cell that has undergone tumorigenic transformation as a result of genetic mutations. This transformed cell is the cell-of-origin for the tumor. In contrast, an established clinical tumor is sustained by subpopulations of self-renewing cancer cells operationally called cancer stem cells (CSC) that can generate, intraclonally, both tumorigenic and nontumorigenic cells. Identifying and characterizing tumor cell-of-origin and CSCs should help elucidate tumor cell heterogeneity, which, in turn, should help understand tumor cell responses to clinical treatments, drug resistance, tumor relapse, and metastatic spread. Both tumor transplantation and lineage-tracing assays have been helpful in characterizing these cancer cell populations, although each system has its strengths and caveats. In this article, we briefly review and summarize advantages and limitations of both assays in support of a combinatorial approach to accurately define the roles of both cancer-initiating and cancer-propagating cells. As an aside, we also wish to clarify the definitions of cancer cell-of-origin and CSCs, which are often interchangeably used by mistake. Cancer Res; 75(19); 4003-11. Ó2015 AACR.

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

“…The cell of origin, or cancer-initiating cell, is considered to be the normal cell that receives the first cancercausing mutation 37,38 . On the other hand, cancer stem cells (CSCs) are the cells that sustain tumour growth and propagation 37,38 .…”

“…On the other hand, cancer stem cells (CSCs) are the cells that sustain tumour growth and propagation 37,38 . The phenotype of cell of origin and CSCs might therefore be substantially different 37,38 . CCAs of different locations exhibit pronounced hetero geneity, raising the question of potential diverse cellular origins in every type of CCA 17 .…”

Problems of Cancer Treatment. Part I. Theory of Treatment Based on Known Mechanisms of Anticancer Immunological Responses

“…Its activity can be inhibited using CIMAvax vaccine, taking advantage of the antibody specific for EGFR [89]. Until now, few recognised epitopes of cancer cells were described [121], such as, for example, peptides in patients with melanoma [21,46] and in ovarian cancer [114]. Due to mutations taking place in cancer cells development of a solid tumour is accompanied relatively dynamic appearance of new antigens, changes in surface markers develop or the antigens become masked.…”

Mechanisms of tumor cell resistance to the current targeted-therapy agents

“…This transition is the result of different mutations in the genome, which converted the origin normal cell to an unusual tumor cell. Moreover, an established tumor is persistent by several subpopulations of cells that are selfrenewing (CSC) and can generate tumorigenic cells [107,108]. The heterogeneity of tumor cells has been described in natural resistance section.…”