Stromal Integrin α11β1 Affects RM11 Prostate and 4T1 Breast Xenograft Tumors Differently

PLoS One. 2016 Mar 18;11(3):e0151663. doi: 10.1371/journal.pone.0151663. eCollection 2016.

Abstract

Purpose: It has been implied that the collagen binding integrin α11β1 plays a role in carcinogenesis. As still relatively little is known about how the stromal integrin α11β1 affects different aspects of tumor development, we wanted to examine the direct effects on primary tumor growth, fibrosis, tumor interstitial fluid pressure (PIF) and metastasis in murine 4T1 mammary and RM11 prostate tumors, using an in vivo SCID integrin α11-deficient mouse model.

Methods: Tumor growth was measured using a caliper, PIF by the wick-in-needle technique, activated fibroblasts by α-SMA immunofluorescence staining and fibrosis by transmission electron microscopy and picrosirius-red staining. Metastases were evaluated using hematoxylin and eosin stained sections.

Results: RM11 tumor growth was significantly reduced in the SCID integrin α11-deficient (α11-KO) compared to in SCID integrin α11 wild type (WT) mice, whereas there was no similar effect in the 4T1 tumor model. The 4T1 model demonstrated an alteration in collagen fibril diameter in the integrin α11-KO mice compared to WT, which was not found in the RM11 model. There were no significant differences in the amount of activated fibroblasts, total collagen content, collagen organization or PIF in the tumors in integrin α11-deficient mice compared to WT mice. There was also no difference in lung metastases between the two groups.

Conclusion: Deficiency of stromal integrin α11β1 showed different effects on tumor growth and collagen fibril diameter depending on tumor type, but no effect on tumor PIF or development of lung metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Animals
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Collagen / metabolism*
  • Female
  • Heterografts
  • Integrins / biosynthesis
  • Integrins / genetics*
  • Lung Neoplasms / secondary
  • Male
  • Mammary Neoplasms, Animal / pathology*
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Microscopy, Electron, Transmission
  • Prostatic Neoplasms / pathology*
  • Receptors, Collagen / biosynthesis
  • Receptors, Collagen / genetics*
  • Tumor Burden / genetics

Substances

  • Actins
  • Integrins
  • Receptors, Collagen
  • integrin alpha11beta1
  • Collagen

Grant support

This work was supported by The Research Council of Norway, grants 223250/F50 to Center of Cancer Biomarkers, University of Bergen; Helse-Vest, NO, grant number 911708-Inga Reigstad; and Helse-Vest, NO, grant number 911966—Rolf K. Reed. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.