ArticleBreast cancer research : BCR2016
The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis.
Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Exploratory analysis of the human breast DNA methylation profile upon soymilk exposure.Scientific reports · 2018Trial
- Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.Journal of translational medicine · 2017Trial
- Mutant p53 sensitizes KRAS-driven lung adenocarcinoma to immunotherapy by repressing SPP1.Science advances · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Bone Metastasis in Estrogen Receptor-Positive Breast Cancer: Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2026Review
- Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment.Cancer research · 2025Review
- Review
- The role of tumor microenvironment and self-organization in cancer progression: Key insights for therapeutic development.BioImpacts : BI · 2025Review
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.PLoS genetics · 2024Article
- Article
- Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer.Archives of medical science : AMS · 2024Article
- The obesity paradox in multiple myeloma: A report from Multiple Myeloma Research Foundation (MMRF) dataset.Cancer medicine · 2023Article
- Deletion of osteopontin in non-small cell lung cancer cells affects bone metabolism by regulating miR-34c/Notch1 axis: a clue to bone metastasis.European journal of histochemistry : EJH · 2023Article
- Genome-wide DNA methylation changes upon DOT1L inhibition in hormone-responsive breast cancer cells.Frontiers in cell and developmental biology · 2023Article
- Cancer-associated fibroblasts in breast cancer: Challenges and opportunities.Cancer communications (London, England) · 2022Review
- Cancer-Associated Fibroblast Subpopulations With Diverse and Dynamic Roles in the Tumor Microenvironment.Molecular cancer research : MCR · 2022Review
- CircRNA circTIAM1 promotes papillary thyroid cancer progression through the miR-646/HNRNPA1 signaling pathway.Cell death discovery · 2022Article
- Pancreatic Tumor Microenvironment Factor Promotes Cancer Stemness via SPP1-CD44 Axis.Gastroenterology · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe tumor microenvironment has complex effects in cancer pathophysiology that are not fully understood. Most cancer therapies are directed against malignant cells specifically, leaving pro-malignant signals from the microenvironment unaddressed. Defining specific mechanisms by which the tumor microenvironment contributes to breast cancer metastasis may lead to new therapeutic approaches against advanced breast cancer.
methodsWe use a novel method for manipulating three-dimensional mixed cell co-cultures, along with studies in mouse xenograft models of human breast cancer and a histologic study of human breast cancer samples, to investigate how breast cancer-associated fibroblasts affect the malignant behaviors of breast cancer cells.
resultsAltering fibroblast Tiam1 expression induces changes in invasion, migration, epithelial-mesenchymal transition, and cancer stem cell characteristics in associated breast cancer cells. These changes are both dependent on fibroblast secretion of osteopontin and also long-lasting even after cancer cell dissociation from the fibroblasts, indicating a novel Tiam1-osteopontin pathway in breast cancer-associated fibroblasts. Notably, inhibition of fibroblast osteopontin with low doses of a novel small molecule prevents lung metastasis in a mouse model of human breast cancer metastasis. Moreover, fibroblast expression patterns of Tiam1 and osteopontin in human breast cancers show converse changes correlating with invasion, supporting the hypothesis that this pathway in tumor-associated fibroblasts regulates breast cancer invasiveness in human disease and is thus clinically relevant.
conclusionsThese findings suggest a new therapeutic paradigm for preventing breast cancer metastasis. Pro-malignant signals from the tumor microenvironment with long-lasting effects on associated cancer cells may perpetuate the metastatic potential of developing cancers. Inhibition of these microenvironment signals represents a new therapeutic strategy against cancer metastasis that enables targeting of stromal cells with less genetic plasticity than associated cancer cells and opens new avenues for investigation of novel therapeutic targets and agents.
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