TY - JOUR
T1 - Regulation of breast cancer response to chemotherapy by fibulin-1
AU - Pupa, Serenella M.
AU - Giuffré, Sarah
AU - Castiglioni, Fabio
AU - Bertola, Lorenzo
AU - Cantú, Marco
AU - Bongarzone, Italia
AU - Baldassari, Paola
AU - Mortarini, Roberta
AU - Argraves, W. Scott
AU - Anichini, Andrea
AU - Menard, Sylvie
AU - Tagliabue, Elda
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-06-4162
DO - 10.1158/0008-5472.CAN-06-4162
M3 - Article
C2 - 17483339
AN - SCOPUS:34249303115
VL - 67
SP - 4271
EP - 4277
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 9
ER -