Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells

Hanna S. Kuznetsov, Timothy Marsh, Beth A. Markens, Zafira Castaño, April Greene-Colozzi, Samantha A. Hay, Victoria E. Brown, Andrea L. Richardson, Sabina Signoretti, Elisabeth M. Battinelli, Sandra S. McAllister

Research output: Contribution to journalArticlepeer-review

Abstract

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC 'instigators') establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors ('responders'). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2+ tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. SIGNIFICANCE: Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it diffi cult to accurately predict which cancer patients are likely to relapse. Our fi ndings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefi t from adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)1150-1165
Number of pages16
JournalCancer discovery
Volume2
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow-derived cells'. Together they form a unique fingerprint.

Cite this