The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation
Open accessAbstract
The chemokine CXCL12 has been shown to regulate breast tumor growth, however, its mechanism in initiating distant metastasis is not well understood. Here, we generated a novel conditional allele of Cxcl12 in mice and used a fibroblast-specific Cre transgene along with various mammary tumor models to evaluate CXCL12 function in the breast cancer metastasis. Ablation of CXCL12 in stromal fibroblasts of mice significantly delayed the time to tumor onset and inhibited distant metastasis in different mouse models. Elucidation of mechanisms using in vitro and in vivo model systems revealed that CXCL12 enhances tumor cell intravasation by increasing vascular permeability and expansion of a leaky tumor vasculature. Furthermore, our studies revealed CXCL12 enhances permeability by recruiting endothelial precursor cells and decreasing endothelial tight junction and adherence junction proteins. High expression of stromal CXCL12 in large cohort of breast cancer patients was directly correlated to blood vessel density and inversely correlated to recurrence and overall patient survival. In addition, our analysis revealed that stromal CXCL12 levels in combination with number of CD31+ blood vessels confers poorer patient survival compared to individual protein level. However, no correlation was observed between epithelial CXCL12 and patient survival or blood vessel density. Our findings describe the novel interactions between fibroblasts-derived CXCL12 and endothelial cells in facilitating tumor cell intrvasation, leading to distant metastasis. Overall, our studies indicate that cross-talk between fibroblast-derived CXCL12 and endothelial cells could be used as novel biomarker and strategy for developing tumor microenvironment based therapies against aggressive and metastatic breast cancer.
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“Various observations highlight activities of TGF-β on endothelial cells that may promote or repress angiogenesis, depending on the experimental setting264–266.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [264]
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Isolation of Putative Progenitor Endothelial Cells for Angiogenesis
Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., & Isner, J. M. (1997) · Science · doi:10.1126/science.275.5302.964 · Cited by 8,725
Tumor Angiogenesis and Metastasis — Correlation in Invasive Breast Carcinoma
Weidner, N., Semple, J. P., Welch, W. R., & Folkman, J. (1991) · New England Journal of Medicine · doi:10.1056/nejm199101033240101 · Cited by 5,598
Involvement of chemokine receptors in breast cancer metastasis
Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., et al. (2001) · Nature · doi:10.1038/35065016 · Cited by 5,340
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632 · cited 1×
“These secretomes can directly engage tumor cells, but can also reprogram other cell types in the TME, including macrophages, immune cells and endothelial cells to indirectly impact tumor cell invasion and metastasis [7].”
Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759
Metastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2622 · Cited by 2,716
Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J. M., & Asahara, T. (1999) · Nature Medicine · doi:10.1038/7434 · Cited by 2,421
Nagasawa, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S.-I., Kitamura, Y., Yoshida, N., Kikutani, H., & Kishimoto, T. (1996) · Nature · doi:10.1038/382635a0 · Cited by 2,382
Feig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100
Weidner, N., Folkman, J., Pozza, F., Bevilacqua, P., Allred, E. N., Moore, D. H., Meli, S., & Gasparini, G. (1992) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/84.24.1875 · Cited by 1,776
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Metadata
- Authors
- Ahirwar, D. K., Nasser, M. W., Ouseph, M. M., Elbaz, M., Cuitiño, M. C., Kladney, R. D., Varikuti, S., Kaul, K., Satoskar, A. R., Ramaswamy, B., Zhang, X., Ostrowski, M. C., Leone, G., & Ganju, R. K.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Leone, Gustavo
- Ganju, Ramesh K.
- ORCID
- Venue
- Oncogene
- Published
- 2018-05-03
- Volume
- 37
- Issue
- 32
- Pages
- 4428-4442
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC7063845
- OpenAlex
- W2800801906
- Cited by
- 162
- References
- 36
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 35 · 2023: 12 · 2022: 13 · 2021: 23 · 2020: 18 · 2019: 17 · 2018: 12
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- Ohio State University
- Pelotonia
- National Cancer Institute (R01CA153490, R01CA109527, P01CA097189)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- CXCL12, breast cancer metastasis, tumor cell intravasation, tumor stromal fibroblasts, vascular permeability, tumor vasculature, endothelial progenitor cells, endothelial tight junctions, blood vessel density, patient survival, tumor microenvironment, conditional alleles
- MeSH terms
- Animals, Breast Neoplasms, Cell Line, Cell Movement, Female, Fibroblasts, Mice, Transgenic, Neoplasm Invasiveness, Neoplasm Metastasis, Mammary Neoplasms, Animal, Endothelial Cells, Cell Line, Tumor, Mice, Chemokine CXCL12, Tumor Microenvironment
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