Regulation of breast cancer response to chemotherapy by fibulin-1.

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.
Authors	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
Journal	Cancer research (Cancer Res) Vol. 67 Issue 9 Pg. 4271-7 (May 01 2007) ISSN: 0008-5472 [Print] United States
PMID	17483339 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibiotics, Antineoplastic Calcium-Binding Proteins Extracellular Matrix Proteins RNA, Small Interfering fibulin Doxorubicin
Topics	Animals Antibiotics, Antineoplastic (pharmacology) Breast Neoplasms (drug therapy, pathology) Calcium-Binding Proteins (antagonists & inhibitors, genetics, physiology) Cell Line, Tumor Cell Survival (drug effects) Doxorubicin (pharmacology) Extracellular Matrix (drug effects, metabolism) Extracellular Matrix Proteins (metabolism) Humans Mice Mice, Inbred BALB C Mice, Nude RNA, Small Interfering (genetics) Transfection

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