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αv-Integrin isoform expression in primary human tumors and brain metastases


Vogetseder, A; Thies, S; Ingold, B; Roth, P; Weller, M; Schraml, P; Goodman, S L; Moch, H (2013). αv-Integrin isoform expression in primary human tumors and brain metastases. International Journal of Cancer, 133(10):2362-2371.

Abstract

PURPOSE: To determine whether metastasis to brain is associated with altered expression patterns of integrins, we investigated the expression of αvβ3, αvβ5, αvβ6 and αvβ8 integrins in primary malignancies and metastases to brain of breast, lung and renal carcinomas and in malignant melanoma. Inhibitors of αv integrins are currently in clinical trials for glioblastoma. The role of integrins in the process of brain metastasis from other human tumors is unknown. EXPERIMENTAL DESIGN: Immunohistochemistry with novel integrin subtype specific rabbit monoclonal antibodies was performed on tissue microarrays of archival material of surgical biopsies taken from primary tumors and brain metastases. RESULTS: Integrin αvβ3 expression was increased in brain metastases compared to primary tumors of breast adenocarcinoma, non-small cell lung cancer, renal clear cell cancer and malignant cutaneous melanoma (all p<0.01). Similarly integrin αvβ8 expression was increased in brain metastases compared to primary tumors of breast cancer (p<0.0001), lung cancer (p<0.01) and renal cancer (p<0.0001), with a similar trend in metastatic melanoma. Integrin αvβ5 was expressed in most primary tumors (98% breast cancer; 67% lung cancer; 90% renal cancer; 89% melanoma) and showed a stronger expression in brain metastases compared to primary tumors from lung cancer and melanoma (p<0.05). Also integrin αvβ6 expression was increased in brain metastases compared to primary breast cancer (p<0.001). CONCLUSIONS: The stronger αv integrin expression in brain metastases, especially of αvβ3 and αvβ8 integrins, suggests that certain αv integrin are involved in the process of brain metastasis. αv integrins may be therapeutic targets for patients with metastatic cancer in brain. © 2013 Wiley Periodicals, Inc.

PURPOSE: To determine whether metastasis to brain is associated with altered expression patterns of integrins, we investigated the expression of αvβ3, αvβ5, αvβ6 and αvβ8 integrins in primary malignancies and metastases to brain of breast, lung and renal carcinomas and in malignant melanoma. Inhibitors of αv integrins are currently in clinical trials for glioblastoma. The role of integrins in the process of brain metastasis from other human tumors is unknown. EXPERIMENTAL DESIGN: Immunohistochemistry with novel integrin subtype specific rabbit monoclonal antibodies was performed on tissue microarrays of archival material of surgical biopsies taken from primary tumors and brain metastases. RESULTS: Integrin αvβ3 expression was increased in brain metastases compared to primary tumors of breast adenocarcinoma, non-small cell lung cancer, renal clear cell cancer and malignant cutaneous melanoma (all p<0.01). Similarly integrin αvβ8 expression was increased in brain metastases compared to primary tumors of breast cancer (p<0.0001), lung cancer (p<0.01) and renal cancer (p<0.0001), with a similar trend in metastatic melanoma. Integrin αvβ5 was expressed in most primary tumors (98% breast cancer; 67% lung cancer; 90% renal cancer; 89% melanoma) and showed a stronger expression in brain metastases compared to primary tumors from lung cancer and melanoma (p<0.05). Also integrin αvβ6 expression was increased in brain metastases compared to primary breast cancer (p<0.001). CONCLUSIONS: The stronger αv integrin expression in brain metastases, especially of αvβ3 and αvβ8 integrins, suggests that certain αv integrin are involved in the process of brain metastasis. αv integrins may be therapeutic targets for patients with metastatic cancer in brain. © 2013 Wiley Periodicals, Inc.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:21 May 2013 08:41
Last Modified:05 Apr 2016 16:47
Publisher:Wiley-Blackwell
ISSN:0020-7136
Publisher DOI:https://doi.org/10.1002/ijc.28267
PubMed ID:23661241
Permanent URL: https://doi.org/10.5167/uzh-78108

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