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

Abstract

PurposeIt 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.MethodsTumor 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.ResultsRM11 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.ConclusionDeficiency 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.

The composition of prostate core matrisome in vivo and in vitro unveiled by mass spectrometric analysis

“…Furthermore, we have previously shown that the expression levels of another collagen receptor, α11β1 integrin, increase during prostate cancer progression . Experiments with α11 integrin null mice have also confirmed the essential function of this receptor during the growth of prostate cancer xenografts …”

“…10 Experiments with α11 integrin null mice have also confirmed the essential function of this receptor during the growth of prostate cancer xenografts. 11 All cell types that are present in the prostate may participate in the production and modulation of the surrounding ECM. However, in normal tissue fibroblast-like cells and in tumors activated myofibroblasts, also called as cancer associated fibroblasts (CAFs), have been suspected to be the major producer and modulator of the ECM.…”

Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis

“…In cells, ITGA11 is involved in collagen-mediated biological processes, such as cell migration, collagen deposition and collagen recombination (41). ITGA11 is highly expressed in esophageal squamous cell carcinoma, head and neck squamous carcinoma, prostate cancer and breast cancer, and is closely associated with the migration and invasion of tumor cells (42)(43)(44). In lung adenocarcinoma A549, H460 and H520 cell lines, tumor growth was significantly higher in A549+WT, compared with A549+Knockout (KO) tumors (45).…”

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine‐19 MRI cell tracking

“…Female BALB/c mice (6-7 weeks; Charles River Canada) were obtained and cared for in accordance with the standards of the Canadian Council on Animal Care under an approved protocol by the Animal Use Subcommittee of Western University's Council on Animal Care. Mice were anesthetized with isoflurane administered at 2% in oxygen, followed by an injection of 300,000 4T1 (n ¼ 26), 168FARN (n ¼ 13), or 67NR (n ¼ 12) cells ( > 90% viability, measured using the trypan blue exclusion assay) suspended in 50 mL Hanks balanced salt solution into the fourth (inguinal) mammary fat pad, as previously reported (29,30). After the procedure, animals were observed until alert and active, when they were returned to their cages.…”