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. 2012 Mar-Apr;6(2):71-7.
doi: 10.4161/cam.20077. Epub 2012 Mar 1.

β1 integrin: an emerging player in the modulation of tumorigenesis and response to therapy

Grant A Howe  1 , Christina L Addison
Affiliations

β1 integrin: an emerging player in the modulation of tumorigenesis and response to therapy

Grant A Howe et al. Cell Adh Migr. 2012 Mar-Apr.

Abstract

Historically, a hallmark of tumorigenesis was the ability to grow in an anchorage-independent manner. Hence, tumors were thought to proliferate and survive independently of integrin attachment to the substratum. However, recent data suggest that integrins regulate not only tumor cell proliferation, survival and migration, but may also influence their response to anti-cancer agents. Interestingly, these influences are largely masked by growth of tumor cells in the standard, yet artificial, environment of 2D cell culture, but are readily apparent under 3D in vitro culture conditions and in tumor growth in vivo. We, and others, have recently demonstrated that the β1 integrin subunit controls the growth and invasion of prostate tumor cells in 3D culture conditions. Recently, the importance of integrins has also been demonstrated using tissue specific conditional knockout strategies in transgenic mouse tumor models, where they control primary tumor growth and dictate the site of metastatic spread. Furthermore, integrin-extracellular matrix interactions may modulate the response of tumors to standard chemotherapy agents or radiation. Taken together, these results highlight the important role of integrins in regulating tumor growth and metastasis; however, point out that the evaluation of their contribution to these processes requires appropriate contextual modeling.

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Figures

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Figure 1. Tumor cell growth in 2D vs. 3D results in differential integrin sublocalization. Cells grown in 2D tissue culture form monolayers which result in fewer cell-cell contact points, and the clustering of integrins and their associated signal transduction molecules at sites of focal adhesion contacts between the cells and the culture surface. In contrast, growth in 3D promotes cell growth in clusters or spheroids whereby cell-cell contacts are increased, and integrins are not clustered at sites of focal contacts, but may be more dispersed across the cell membrane in association with ECM proteins at a multitude of points. This lack of integrin clustering likely leads to different signal transduction events in cells grown in 3D as compared with those grown in 2D and hence may render the cell more dependent on ECM engagement by integrins to overcome anoikis.
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Comment on

  • Schooley AM, Andrews NM, Zhao H, Addison CL. β1 integrin is required for anchorage-independent growth and invasion of tumor cells in a context dependent manner. Cancer Lett. 2012;316:157–67. doi: 10.1016/j.canlet.2011.10.032.

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