Quantification of tumor virulence based upon competition between dissimilar subcultured cancer cell lines

Philip Weintraub

doi:10.1097/ij9.0000000000000096

Abstract

Purpose: A direct quantitative metric that represents the intrinsic virulent properties of a particular tumor is absent, and the development of such a numeric modifier would balance the disproportionate weight of qualitative elements that presently monopolize the nomenclature of cancer. To address this shortcoming, an in vitro model was developed to study the competitive nature of dissimilar cancer cell lines. Methods: A prospective series of surgically excised and pathologically confirmed malignant tumors were separated from their adherent state and subcultured according to international standards. After a total of 7 different tumor cell lines were established, each cell line was paired with a dissimilar cancer cell line, and by using all possible combinations, a total of 21 unique tumor pairs were assessed over 7 days after plating on diametrically opposed sections of gridded Petri dishes containing enriched growth medium. Each dish was then examined for changes in tumor cell position on the grid, and a scoring system was established that awarded points for aggressive behaviors. Results: Ovarian cancer, lymphoma, and lung cancers demonstrated overall dominance, with wins in at least 2/3 of their matches. Breast and kidney cancers were intermediate in performance, and gastric and colon cancers were subordinate in the majority of their matches. Discussion: This pilot experiment revealed that intercellular competition exists between previously untreated, subcultured, and dissimilar tumor cells in this in vitro assay. Moreover, such intercellular competition and the unilateral dominance of specific cancer tissue types have not been previously reported in the literature.

Highlights

The TNM classification of cancer is based on the identification of specific histopathologic cancer cell types as well as their origin and invasion into the surrounding tissues, local lymphatic vessels, or distant sites within the human host
Cancer cells become independent of these homeostatic controls via deregulation of extracellular signals, and these signals are typically mediated by the interaction of growth factors with cell-surface receptors, which frequently contain intracellular tyrosine kinase domains
In the matched-pair competitions (Table 3), the following were observed: lymphoma overwhelmed ovarian cancer, lung cancer dominated lymphoma, and ovarian cancer, victorious over kidney and colon cancer, achieved these victories by narrow margins. These results indicated the occurrence of relative dominance, as opposed to absolute dominance, with a dominant cell line toward one cell type falling victim to a second cancer cell line of relative lesser dominance, suggesting that there are potentially multiple cellular factors influencing the outcome of each pairing

Summary

Introduction

The TNM classification of cancer is based on the identification of specific histopathologic cancer cell types as well as their origin and invasion into the surrounding tissues, local lymphatic vessels, or distant sites within the human host. The gene-related transformation of normal cells into a super-competitor state might come at the expense of the surrounding tissue within the tumor microenvironment. The induction of apoptosis in adjacent cells might benefit the predominant tumor cells, the total cell number may remain constant[3,4] This phenomenon has been postulated to occur in the early stages of malignant transformation and to potentially account for clinical observations, such as “field cancerization.”. Intercellular and intracellular communications are generally thought to play central roles in malignant transformation and carcinogenesis, and the biochemical responses of cells to such stimuli in their extracellular microenvironments serve to regulate the intricate biological processes of proliferation, migration, and apoptosis. There is little insight into the mechanisms that control cellular proliferation and the release of mitogenic signals[7]

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