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Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression.
Clin Cancer Res. 2004 Nov 01; 10(21):7335-46.CC

Abstract

PURPOSE

The aim of this study was to characterize phenotypic alterations along the progression of breast carcinoma from primary tumor to pleural effusion through analysis of the expression of proteases, laminin receptors (LRs), and transcription factors involved in invasion and metastasis.

EXPERIMENTAL DESIGN

The material studied consisted of 60 malignant pleural effusions from breast cancer patients and 68 corresponding solid tumors (37 primary and 31 metastatic tumors). Expression of matrix metalloproteinases [MMPs (MMP-1, MMP-2, MMP-9, and MMP-14)], the MMP inhibitor tissue inhibitor of metalloproteinase-2, the MMP inducer EMMPRIN, the 67-kDa LR, the alpha6 integrin subunit, and the transcription factors AP-2, Ets-1, and PEA3 was studied using immunohistochemistry, mRNA in situ hybridization, reverse transcription-polymerase chain reaction, zymography, and flow cytometry. Hormone receptor (estrogen receptor and progesterone receptor) status and c-erbB-2 status were also studied.

RESULTS

Significantly reduced estrogen receptor (P < 0.001) and progesterone receptor (P = 0.001) expression was seen in effusions compared with primary tumors, with opposite findings for c-erbB-2 (P = 0.003). Tumor cell MMP-2 protein expression in effusions was higher than that in primary tumors (P < 0.001) and lymph node metastases (P = 0.01). In situ hybridization demonstrated higher MMP-2 (P = 0.007), PEA3 (P = 0.038), and EMMPRIN (P = 0.026) mRNA expression in effusions. The time to progression from primary tumor to effusion was significantly shorter for patients whose primary tumors expressed MMP-1 (P = 0.016) and who expressed the 67-kDa LR protein in primary tumor (P = 0.007) and effusion (P = 0.015).

CONCLUSIONS

Our data provide documented evidence of molecular events that occur during the progression of breast carcinoma from primary tumor to effusion. The coordinated up-regulation of MMP-2 and Ets transcription factors in carcinoma cells in effusions is in full agreement with our previous reports linking these factors to poor prognosis in ovarian cancer. The rapid progression to effusion in cases showing MMP-1 and 67-kDa LR expression in primary tumor cells links aggressive clinical behavior with expression of metastasis-associated molecules in this setting.

Authors+Show Affiliations

Davidson B
Department of Pathology, The Norwegian Radium Hospital, Montebello, University of Oslo, Oslo, Norway. davidsob@mail.nih.gov
Konstantinovsky S
No affiliation info available
Nielsen S
No affiliation info available
Dong HP
No affiliation info available
Berner A
No affiliation info available
Vyberg M
No affiliation info available
Reich R
No affiliation info available

MeSH

AdultAgedBreast NeoplasmsCell Line, TumorDisease ProgressionFemaleFlow CytometryHumansImmunohistochemistryIn Situ HybridizationLymphatic MetastasisMiddle AgedModels, BiologicalNeoplasm InvasivenessNeoplasm MetastasisRNA, MessengerReceptor, ErbB-2Receptors, EstrogenReceptors, LamininReceptors, ProgesteroneReverse Transcriptase Polymerase Chain ReactionTime FactorsUp-Regulation

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15534110

Citation

Davidson, Ben, et al. "Altered Expression of Metastasis-associated and Regulatory Molecules in Effusions From Breast Cancer Patients: a Novel Model for Tumor Progression." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 10, no. 21, 2004, pp. 7335-46.
Davidson B, Konstantinovsky S, Nielsen S, et al. Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression. Clin Cancer Res. 2004;10(21):7335-46.
Davidson, B., Konstantinovsky, S., Nielsen, S., Dong, H. P., Berner, A., Vyberg, M., & Reich, R. (2004). Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 10(21), 7335-46.
Davidson B, et al. Altered Expression of Metastasis-associated and Regulatory Molecules in Effusions From Breast Cancer Patients: a Novel Model for Tumor Progression. Clin Cancer Res. 2004 Nov 1;10(21):7335-46. PubMed PMID: 15534110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression. AU - Davidson,Ben, AU - Konstantinovsky,Sophya, AU - Nielsen,Søren, AU - Dong,Hiep Phuc, AU - Berner,Aasmund, AU - Vyberg,Mogens, AU - Reich,Reuven, PY - 2004/11/10/pubmed PY - 2005/5/4/medline PY - 2004/11/10/entrez SP - 7335 EP - 46 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 10 IS - 21 N2 - PURPOSE: The aim of this study was to characterize phenotypic alterations along the progression of breast carcinoma from primary tumor to pleural effusion through analysis of the expression of proteases, laminin receptors (LRs), and transcription factors involved in invasion and metastasis. EXPERIMENTAL DESIGN: The material studied consisted of 60 malignant pleural effusions from breast cancer patients and 68 corresponding solid tumors (37 primary and 31 metastatic tumors). Expression of matrix metalloproteinases [MMPs (MMP-1, MMP-2, MMP-9, and MMP-14)], the MMP inhibitor tissue inhibitor of metalloproteinase-2, the MMP inducer EMMPRIN, the 67-kDa LR, the alpha6 integrin subunit, and the transcription factors AP-2, Ets-1, and PEA3 was studied using immunohistochemistry, mRNA in situ hybridization, reverse transcription-polymerase chain reaction, zymography, and flow cytometry. Hormone receptor (estrogen receptor and progesterone receptor) status and c-erbB-2 status were also studied. RESULTS: Significantly reduced estrogen receptor (P < 0.001) and progesterone receptor (P = 0.001) expression was seen in effusions compared with primary tumors, with opposite findings for c-erbB-2 (P = 0.003). Tumor cell MMP-2 protein expression in effusions was higher than that in primary tumors (P < 0.001) and lymph node metastases (P = 0.01). In situ hybridization demonstrated higher MMP-2 (P = 0.007), PEA3 (P = 0.038), and EMMPRIN (P = 0.026) mRNA expression in effusions. The time to progression from primary tumor to effusion was significantly shorter for patients whose primary tumors expressed MMP-1 (P = 0.016) and who expressed the 67-kDa LR protein in primary tumor (P = 0.007) and effusion (P = 0.015). CONCLUSIONS: Our data provide documented evidence of molecular events that occur during the progression of breast carcinoma from primary tumor to effusion. The coordinated up-regulation of MMP-2 and Ets transcription factors in carcinoma cells in effusions is in full agreement with our previous reports linking these factors to poor prognosis in ovarian cancer. The rapid progression to effusion in cases showing MMP-1 and 67-kDa LR expression in primary tumor cells links aggressive clinical behavior with expression of metastasis-associated molecules in this setting. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15534110/Altered_expression_of_metastasis_associated_and_regulatory_molecules_in_effusions_from_breast_cancer_patients:_a_novel_model_for_tumor_progression_ DB - PRIME DP - Unbound Medicine ER -