Ecology meets cancer biology: the cancer swamp promotes the lethal cancer phenotype.

Sarah R Amend,Kenneth J Pienta

doi:10.18632/oncotarget.3430

Abstract

As they grow, tumors fundamentally alter their microenvironment, disrupting the homeostasis of the host organ and eventually the patient as a whole. Lethality is the ultimate result of deregulated cell signaling and regulatory mechanisms as well as inappropriate host cell recruitment and activity that lead to the death of the patient. These processes have striking parallels to the framework of ecological biology: multiple interacting ecosystems (organ systems) within a larger biosphere (body), alterations in species stoichiometry (host cell types), resource cycling (cellular metabolism and cell-cell signaling), and ecosystem collapse (organ failure and death). In particular, as cancer cells generate their own niche within the tumor ecosystem, ecological engineering and autoeutrophication displace normal cell function and result in the creation of a hypoxic, acidic, and nutrient-poor environment. This "cancer swamp" has genetic and epigenetic effects at the local ecosystem level to promote metastasis and at the systemic host level to induce cytokine-mediated lethal syndromes, a major cause of death of cancer patients.

Highlights

It has long been appreciated that cancer is a disease of the whole organism, requiring the proliferation of malignant cells and the participation of host cells and signaling factors [1, 2]
Cancer cells act as an invasive species as they expand within the host ecosystem as a primary tumor and again later as they colonize a distant site as a metastasis [9, 16]
Without the selective pressure of the engineered ecosystem, the cancer cells are much more likely to remain restrained to www.impactjournals.com/oncotarget the primary tumor rather than metastasize to distant sites

Summary

Introduction

It has long been appreciated that cancer is a disease of the whole organism, requiring the proliferation of malignant cells and the participation of host cells and signaling factors [1, 2]. Ecology principles describe the enabling characteristics of the tumor microenvironment, including the factors that promote selection of aggressive traits in malignant disease as well as the local and systemic impact of cancer cells on the native host.

Results

Conclusion