Inflammation induced by breast cancer chemotherapy awakens dormant cancer cells

Bad or good news! Cancer is history (soon)!

"... In [t]his latest study ... ask a critical question: What causes these dormant cancer cells to erupt into a frenzy of growth and division? ..."

From the significance and abstract:

"Significance

Breast cancer often reveals its life-threatening effects after disseminated, clinically undetectable dormant cancer cells awaken, generating aggressively growing metastases. ... As shown here, this profound shift can result from inflammation of the tissue microenvironment in which these carcinoma cells are embedded.

Abstract

The awakening of dormant disseminated cancer cells appears to be responsible for the clinical relapses of patients whose primary tumors have been successfully cured months and even years earlier.

In the present study, we demonstrate that dormant breast cancer cells lodged in the lungs reside in a highly mesenchymal, nonproliferative phenotypic state.

The awakening of these cells is not triggered by a cancer cell-autonomous process. Instead, lung inflammation induced by the chemotherapeutic agent bleomycin effectively awakens dormant cancer cells, providing useful models for studying metastatic awakening.

Mechanistically, the awakened cells shift from a highly mesenchymal to a quasi-mesenchymal phenotypic state in which they acquire tumorigenicity and proliferative ability.

Once awakened, these cells can stably reside in this quasi-mesenchymal state and maintain their tumor-initiating ability, doing so without ongoing heterotypic signaling from the lung microenvironment.

Epidermal growth factor receptor ligands released by the cells of the injured tissue microenvironment, including notably M2 type macrophages, promote dormant cancer cells to move toward this quasi-mesenchymal state, a transition that is critical for the awakening process.

An understanding of the mechanisms of metastatic awakening may lead in the future to treatment strategies designed to prevent such awakening and resulting metastatic relapse."

Inflammation jolts “sleeping” cancer cells awake, enabling them to multiply again | MIT News | Massachusetts Institute of Technology "Chemotherapy-induced injury of organ tissue causes inflammation that awakens dormant cancer cells, which may cause new tumors to form."

Inflammation awakens dormant cancer cells by modulating the epithelial–mesenchymal phenotypic state (no public access)

[The legend to this image can be found in the first article above]