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Paracrine Signaling by Platelet-Derived Growth Factor-CC Promotes Tumor Growth by Recruitment of Cancer-Associated Fibroblasts
Open accessAbstract
Cancer results from the concerted performance of malignant cells and stromal cells. Cell types populating the microenvironment are enlisted by the tumor to secrete a host of growth-promoting cues, thus upholding tumor initiation and progression. Platelet-derived growth factors (PDGF) support the formation of a prominent tumor stromal compartment by as of yet unidentified molecular effectors. Whereas PDGF-CC induces fibroblast reactivity and fibrosis in a range of tissues, little is known about the function of PDGF-CC in shaping the tumor-stroma interplay. Herein, we present evidence for a paracrine signaling network involving PDGF-CC and PDGF receptor-alpha in malignant melanoma. Expression of PDGFC in a mouse model accelerated tumor growth through recruitment and activation of different subsets of cancer-associated fibroblasts. In seeking the molecular identity of the supporting factors provided by cancer-associated fibroblasts, we made use of antibody arrays and an in vivo coinjection model to identify osteopontin as the effector of the augmented tumor growth induced by PDGF-CC. In conclusion, we establish paracrine signaling by PDGF-CC as a potential drug target to reduce stromal support in malignant melanoma.
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“Many of the expanding range of receptor tyrosine kinase inhibitors have some activity on FGF and PDGF receptors that can drive fibroblast function148,149.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [148]
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Metadata
- Authors
- Anderberg, C., Li, H., Fredriksson, L., Andrae, J., Betsholtz, C., Li, X., Eriksson, U., & Pietras, K.
- Affiliations
- Ludwig Cancer Research (SE)
- 1Ludwig Institute for Cancer Research Ltd., Stockholm Branch, and
- Karolinska Institutet (SE)
- National Institutes of Health (US)
- Venue
- Cancer Research
- Published
- 2008-12-31
- Volume
- 69
- Issue
- 1
- Pages
- 369-378
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2613547
- OpenAlex
- W2160108544
- Cited by
- 249
- References
- 49
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 16 · 2022: 10 · 2021: 10 · 2020: 15 · 2019: 12 · 2018: 19 · 2017: 17 · 2016: 16 · 2015: 21 · 2014: 18 · 2013: 15 · 2012: 12
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Cancer Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- Cancerfonden
- Karolinska Institutet
- Vetenskapsrådet
- National Institutes of Health (Z99 EY999999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- PDGF-C, paracrine signaling, cancer-associated fibroblasts, tumor microenvironment, tumor stroma, melanoma, PDGF receptor alpha, osteopontin, tumor growth, fibroblast recruitment, stromal support
- MeSH terms
- Animals, Fibroblasts, Humans, Lymphokines, Melanoma, Melanoma, Experimental, Mice, Inbred C57BL, Platelet-Derived Growth Factor, Skin Neoplasms, Signal Transduction, Stromal Cells, Receptor, Platelet-Derived Growth Factor alpha, NIH 3T3 Cells, Cell Line, Tumor, Cell Growth Processes, Mice, Osteopontin
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