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?v-Integrin isoform expression in primary human tumors and brain metastases.

Al's Comment:

Integrins are receptors on the cell membrane that help a cell communicate with it's enviorment.  This article shows that there are various subtypes found on primary and metastatic tumor cells which may open up a new target to use for treatments.  There is an Integrin blocking drug in trials for GBMs now (Cilengitide). Perhaps the trials should be extended to metastatic tumors.The early trials in GBM did not show significantly improved results but I wouldn't write this drug off yet - they need to find the best way to use it. I picture it as part of a cocktail approach.


Posted on: 05/18/2013

Int J Cancer. 2013 May 10. doi: 10.1002/ijc.28267. [Epub ahead of print]
αv-Integrin isoform expression in primary human tumors and brain metastases.
Vogetseder A, Thies S, Ingold B, Roth P, Weller M, Schraml P, Goodman SL, Moch H.
Institute for Surgical Pathology, Department of Pathology, University Hospital, Zurich, Switzerland.
 
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.
 
Copyright © 2013 UICC.
 

 


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