Immunological and pathobiological roles of fibulin-1 in breast cancer (original) (raw)
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Elevated expression and altered processing of fibulin-1 protein in human breast cancer
British journal of cancer, 2003
The extracellular matrix protein fibulin-1 suppresses the motility and invasiveness of a variety of tumour cell types in vitro as well as the growth of fibrosarcoma tumours in nude mice. In this study, fibulin-1 protein expression in breast carcinoma specimens and normal breast tissue was evaluated immunohistologically. Fibulin-1 protein expression was also semiquantitatively assessed by immunoblot analysis in a collection of normal breast tissues (n=18), benign tumours (n=5) and breast carcinomas (n=39). In normal breast tissue, fibulin-1 protein expression predominated in the ductal epithelium and underlying myoepithelium, with weaker staining evident in the loose connective surrounding the ducts. Examination of breast carcinomas revealed that the tumour cells also expressed fibulin-1 protein. The level of mature fibulin-1 polypeptide (100 kDa) was higher in the breast carcinoma specimens as compared to normal breast tissue (Mann-Whitney U-test, P=0.0005). In addition to the matur...
Regulation of Breast Cancer Response to Chemotherapy by Fibulin-1
Cancer Research, 2007
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. [Cancer Res 2007;67(9):4271-7] Materials and Methods Cell lines. Human breast carcinoma cell lines SKBR-3, MCF-7, MDA-MB-157, MDA-MB-231, MDA-MB-361, MDA-MB-468, MDA-MB-453, and MDA-MB-175 were obtained from the American Type Culture Collection (ATCC). The MDA-MB-435 cell line, which shows both breast-specific and melanocyte-specific markers (26), was also obtained from ATCC. Cell lines were routinely maintained in RPMI 1640 (Sigma Chemical Co.) supplemented with 10% (v/v) FCS (Sigma Chemical) and L-glutamine in a humidified chamber (95% air, 5% CO 2 ) at 37jC. Human breast tumor MCF-7-DXR (doxorubicin-resistant variant) and MCF-7B (parental) cell lines were kindly provided by ref. 27].
Loss of Fibulin-2 Expression Is Associated with Breast Cancer Progression
The American Journal of Pathology, 2007
Fibulin-2 , an extracellular matrix protein expressed by normal epithelia , was found to be down-regulated in several breast cancer cell lines. Fibulin-2 protein expression was also decreased in breast cancer tissue samples as evaluated by immunohistochemistry. Reintroduction of Fibulin-2 into breast cancer cell lines that do not express Fibulin-2 reduced cancer cell motility and invasion in vitro but had no effect on cell growth and adhesion properties. Together with evidence that Fibulin-2 contributes to wound healing and inhibits smooth muscle cell migration , our findings suggest that loss of Fibulin-2 expression may facilitate migration and invasion in breast cancer.
Life sciences, 2018
Interaction of Sex Hormone-Binding Globulin (SHBG) with estrogen-sensitive breast cancer cells has a protective role against estrogen exposure. No specific membrane receptor for SHBG had been identified by now, but a putative interaction of SHBG with extracellular matrix associated-proteins (e.g. fibulins) was suggested. In this study we investigated the expression of fibulins, their functional relationship with SHBG and involvement in behavior of estrogen-sensitive breast cancer. Gene expression of fibulins was performed by Real time-PCR on two estrogen-sensitive breast cancer cell lines, MCF-7 and T47D. Fibulin-1 protein expression and localization were determined by Western blot and immunofluorescence. SHBG interaction with-fibulin-1 was assessed by GST-pull down assay. MCF-7 cell growth and gene expression, after fibulin-1 silencing by siRNA, were evaluated. Finally, the expression of fibulin-1 was correlated to clinical and pathological data of 21 breast cancer tissue samples. ...
Clinical importance of fibulin-5 immunohistochemical staining in breast lesions
Polish Journal of Pathology, 2019
The aim of this study was to evaluate the clinical importance of fibulin-5, which has been shown to display tumour-promoting and tumour-protective functions in breast lesions. Sixty-two breast cancer patients, 19 patients with fibroadenoma, and 15 healthy breast tissues were enrolled. Forty-seven patients had invasive ductal carcinoma (IDC) (12 of them also had in situ carcinoma DCIS), and 15 had invasive lobular carcinoma (ILC). A scoring system from 0 to 4 was used to evaluate the fibulin-5 staining according to the percentage of stained cells. The median values of fibulin-5 staining scores of the breast cancer, fibroadenoma, and healthy breast tissues were 2 (range: 0-4), 3 (range: 3-4), and 4 (range: 1-4), respectively, and the difference is statistically significant (p = 0.0001). There was no significant difference between the fibulin-5 scores of IDC, ILC, and DCIS. Fifteen patients with triple-negative breast cancer (TNBC) had the lowest fibulin-5 score (p < 0.0001). The median fibulin-5 scores of the patients according to Ki-67 index ≥ 14% and < 14% were 2 (range: 1-5) and 4 (range: 1-5), respectively, and the difference is statistically significant (p = 0.001). These data can be explained by the inhibitory effect of fibulin-5 on epithelial cell proliferation, which is closely related to differentiation and prognosis.