Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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Oncotarget | Platelet-derived Growth Factor (PDGF) Cross-signaling Via Non-corresponding Receptors Indicates Bypassed Signaling in Colorectal Cancer
FOR IMMEDIATE RELEASE 2022-10-20
“The present study analyzed PDGFR and VEGFR expression in primary colon cancer tissues and CRC cell lines in order to better define their expression profiles. Furthermore, we analyzed putative PDGF cross-binding with VEGFR and EGFR in HT29 cells lacking PDGFR expression.”
Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression.
Previously, researchers Romana Moench, Martin Gasser, Karol Nawalaniec, Tanja Grimmig, Amrendra K. Ajay, Larissa Camila Ribeiro de Souza, Minghua Cao, Yueming Luo, Petra Hoegger, Carmen M. Ribas, Jurandir M. Ribas-Filho, Osvaldo Malafaia, Reinhard Lissner, Li-Li Hsiao, and Ana Maria Waaga-Gasser, from Harvard Medical School, Shenzhen Traditional Chinese Medicine Hospital, University of Wuerzburg, and Mackenzie Evangelical Faculty of Paraná, recently provided evidence for upregulation of PDGF expression in UICC stage I–IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. In their new study, the researchers sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC.
“Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRβ, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors.”
Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. The team then analyzed several CRC cell lines for PDGFRα, PDGFRβ, VEGFR1, and VEGFR2 protein expression. They found these receptors to be variably expressed amongst the investigated cell lines.
Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor.
“Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.”
Keywords: PDGF, VEGFR, EGFR, bypassed signaling, colorectal cancer
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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