The alpha2beta1 integrin is a metastasis suppressor in mouse models and human cancer (J Clin Invest, 2011, 121:226-237)

報告日期: 2011/03/18
報告時間: 17:10/18:00
報告學生: 陳勝義 (英文報告)
講評老師: 鄭宏祺
附件下載:

Full Text:http://basicmed.med.ncku.edu.tw/admin/up_img/0318-3.pdf

The α2β1 integrin is a metastasis suppressor in mouse models and human cancer
 
Norma E. Ramirez, Mary M. Zutter. et al. JCI. 2011; 121: 226-237.
 
Student: 陳勝義
Commentator: 鄭宏祺老師
Time: 17:10-18:00, 2011/03/18
Place: 602教室
 
Abstract
Background:
Cancer progression, including invasion and metastasis, is regulated by cell-cell and cell-matrix interactions1. Previous studies demonstrated that defects in adhesion receptors or alter expression of matrix components could lead to the alteration of cancer progression and metastasis2, 3.      
Objective:
One of the receptors for collagen and other matrix molecules is α2β1 integrin which is highly expressed on normal breast epithelium. Early studies showed that loss of the α2β1 integrin expressionmay enhance malignant progression4. However, contradict findings exist. The α2β1 integrin may promote metastasis to different organs5. Therefore, the authors wanted to explore the role of the α2β1 integrin in cancer initiation and progression.
Results:
In order to determine the role of the α2β1 integrin in breast cancer initiation,progression, and metastasis, the authors crossed the α2β1 integrin–deficientmouse with transgenic animals carrying the MMTV-c-erbB2/Neuoncogene to generate WT/MMTV-Neu (WT/Neu) and α2-null/MMTV-Neu (α2-null/Neu) animals. The data showed that loss of the α2β1 integrin increased breast cancer metastasis and intravasation, but did not alter tumor growth in vivo. In addition, loss of α2β1 integrin expression predicts metastasis and decreased survival in breast cancer patients.
Conclusion:
The authors identifykey mechanistic steps in the metastatic cascade enhanced by lossof α2β1 integrin expression and suggest that the α2β1integrin is a metastasis suppressor of breast cancer.
References
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2.    Plantefaber LC, Hynes RO. Changes in integrinreceptors on oncogenically transformed cells. Cell.1989;56(2):281–290.
3.    Hynes RO. Targeted mutations in cell adhesiongenes: what have we learned from them? Dev Biol.1996;180(2):402–412.
4.    Zutter MM, Mazoujian G, Santoro SA. Decreasedexpression of integrin adhesive protein receptorsin adenocarcinoma of the breast. Am J Pathol.1990;137(4):863–870.
5.    Yoshimura K, et al. Integrin alpha2 mediatesselective metastasis to the liver. Cancer Res. 2009;
69(18):7320–7328.