Modeling the Evolution of Ploidy in a Resource Restricted Environment

Abstract

Gliomas are tumors that evolve from glial cells in the brain or spine. Most gliomas are diagnosed as either lower-grade lesions (grade II) or Glioblastoma (grade IV). Progression of lower-grade gliomas (LGG) to Glioblastoma (GBM) is accompanied by a phenotypic switch to a highly invasive tumor cell phenotype. Converging evidence from different cancer types, including colorectal-, breast-, and lung- cancers, suggests a strong enrichment of high ploidy cells among metastatic lesions as compared to the primary tumor [1, 2]. Even in normal development: trophoblast giant cells - the first cell type to terminally differentiate during embryogenesis - are responsible for invading the placenta and strikingly these cells can have up to 1000 copies of the genome [5]. All this points to the existence of a ubiquitous mechanism that links high DNA content to an invasive phenotype. We formulate a mechanistic Grow-or-go model that postulates higher energy demands of high-ploidy cells as a driver of their invasive behavior. We will test whether this mechanism may contribute to the quick recurrence of GBMs after surgery [7] and whether it can explain striking differences in the prognostic power of integrin signaling and cell cycle progression between males and females [13].

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA215256.