ArticleMolecular cancer research : MCR2012
Loss of TGF-β responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 65 citations in OpenAlex.
- The Significance of CXCL1 in Cancer: An Overview of Molecular Mechanisms.International journal of molecular sciences · 2026Review
- Analysis of the heterogeneity of the immune microenvironment of bone metastases and new strategies of nanotechnology intervention.Oncology reviews · 2026Review
- The role of cancer-associated fibroblasts in the tumour microenvironment of urinary system.Clinical and translational medicine · 2025Review
- ASPORIN: A root of the matter in tumors and their host environment.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- TGFβ1 induces CXCL1 to promote stemness features in lung cancer.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases.Biology · 2023Article
- Dissecting metastasis using preclinical models and methods.Nature reviews. Cancer · 2023Review
- Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.International journal of molecular sciences · 2023Review
- Cancer-Associated Fibroblast Heterogeneity, Activation and Function: Implications for Prostate Cancer.Biomolecules · 2022Review
- Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases.Cancer letters · 2022Article
- Review
- Metastasis-associated fibroblasts: an emerging target for metastatic cancer.Biomarker research · 2021Review
- The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone.International journal of molecular sciences · 2021Review
- The In Vivo Selection Method in Breast Cancer Metastasis.International journal of molecular sciences · 2021Review
- Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation.Journal of immunology research · 2021Review
- Review
- Fibroblast growth factors signaling in bone metastasis.Endocrine-related cancer · 2020Review
- Article
- Article
- Prostate Organogenesis.Cold Spring Harbor perspectives in medicine · 2018Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Loss of TGF-β type II receptor (TβRII, encoded by Tgfbr2) expression in the prostate stroma contributes to prostate cancer initiation, progression, and invasion. We evaluated whether TβRII loss also affected prostate cancer bone metastatic growth. Immunohistologic analysis revealed that TβRII expression was lost in cancer-associated fibroblasts in human prostate cancer bone metastatic tissues. We recapitulated the human situation with a conditional stromal Tgfbr2 knockout (Tgfbr2-KO) mouse model. Conditioned media from primary cultured Tgfbr2-KO or control Tgfbr2-flox prostatic fibroblasts (koPFCM or wtPFCM, respectively) were applied to C4-2B prostate cancer cells before grafting the cells tibially. We found that koPFCM promoted prostate cancer cell growth in the bone and development of early mixed osteoblastic/osteolytic bone lesions. Furthermore, the koPFCM promoted greater C4-2B adhesion to type-I collagen, the major component of bone matrix, compared to wtPFCM-treated C4-2B. Cytokine antibody array analysis revealed that koPFCM had more than two-fold elevation in granulocyte colony-stimulating factor and CXCL1, CXCL16, and CXCL5 expression relative to wtPFCM. Interestingly, neutralizing antibodies of CXCL16 or CXCL1 were able to reduce koPFCM-associated C4-2B type-I collagen adhesion to that comparable with wtPFCM-mediated adhesion. Collectively, our data indicate that loss of TGF-β responsiveness in prostatic fibroblasts results in upregulation of CXCL16 and CXCL1 and that these paracrine signals increase prostate cancer cell adhesion in the bone matrix. These microenvironment changes at the primary tumor site can mediate early establishment of prostate cancer cells in the bone and support subsequent tumor development at the metastatic site.
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