Regulation of breast cancer response to chemotherapy by fibulin-1

Serenella M. Pupa, Sarah Giuffré, Fabio Castiglioni, Lorenzo Bertola, Marco Cantú, Italia Bongarzone, Paola Baldassari, Roberta Mortarini, W. Scott Argraves, Andrea Anichini, Sylvie Menard, Elda Tagliabue

Research output: Contribution to journalArticlepeer-review

Abstract

Doxorubicin treatment was found to augment the expression of the extracellular matrix (ECM) protein fibulin-1 in cultured human breast cancer cell lines and in MDA-MB-361 tumors grown in athymic mice. Doxorubicin was also found to augment tumor expression of the fibulin-1-binding proteins fibronectin and laminin-1. Growth of breast cancer cell lines on Matrigel, an ECM extract containing fibulin-1 and laminin-1, resulted in lower levels of doxorubicin-induced apoptosis as compared with controls. Moreover, tumors formed by injection of athymic mice with MDA-MB-361 cells mixed with Matrigel were significantly more doxorubicin resistant and displayed lower levels of apoptosis compared with those that formed in the absence of Matrigel. Monoclonal antibodies against fibulin-1 reversed Matrigel-dependent doxorubicin resistance. Furthermore, small interfering RNA-mediated suppression of fibulin-1 expression in breast cancer cells resulted in a 10-fold increase in doxorubicin sensitivity as compared with control cells. Together, these findings point to a role for fibulin-1 in breast cancer chemoresistance.

Original languageEnglish
Pages (from-to)4271-4277
Number of pages7
JournalCancer Research
Volume67
Issue number9
DOIs
Publication statusPublished - May 1 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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