uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-β phosphorylation, and microvessel density in gastric cancer
Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
Department of Pathology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
Show others and affiliations
2010 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 10, 659- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Angiogenesis is important in the growth and metastasis of various kinds of solid tumors, including gastric cancers. The angiogenic process is triggered by several key growth factors, including vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF)-B, that are secreted by tumors. Our aim was to define: i) the expression pattern of VEGF-A and PDGF-B in tumor cells and the activation of PDGF receptor (PDGFR)-beta tyrosine kinase in stromal cells of human gastric adenocarcinomas; and ii) the relationship between VEGF-A and PDGF-B expression and microvessel density (MVD), to determine if there is a rationale for a new therapeutic strategy. METHODS: A series of 109 gastric adenocarcinoma cases that had undergone surgical resection was examined immunohistochemically using antibodies against VEGF-A, PDGF-B, and CD34, followed by further examination of PDGFR-beta phosphorylation by immunoblotting analysis. RESULTS: MVD was higher in diffuse-type than intestinal-type cancers (p<0.001). VEGF-A overexpression correlated to PDGF-B overexpression in both the intestinal-type (p<0.005) and diffuse-type (p<0.0001) groups, indicating that VEGF-A and PDGF-B are secreted simultaneously in the same tumor, and may thus play important roles together in angiogenesis. However, several differences between intestinal-type and diffuse-type cancers were observed. In the diffuse-type cancer group, higher MVD was related to the PDGF-B proportion (p<0.05) and VEGF-A overexpression (p<0.05), but not to PDGF-B overexpression or the VEGF-A proportion. On the other hand, in the intestinal-type cancer group, higher MVD was correlated to overexpression (p<0.005), intensity (p<0.05), and proportion (p<0.05) of PDGF-B, but not of VEGF-A. In addition, phosphorylation of PDGFR-beta was correlated with depth of cancer invasion at statistically significant level. CONCLUSIONS: Our results indicate that PDGF-B, which is involved in the maintenance of microvessels, plays a more important role in angiogenesis in intestinal-type gastric carcinomas than VEGF-A, which plays a key role mainly in the initiation of new blood vessel formation. In contrast, VEGF-A has a critical role for angiogenesis more in diffuse-type cancers, but less in those of intestinal type. Thus, a therapy targeting the PDGF-B signaling pathway could be effective for intestinal-type gastric carcinoma, whereas targeting VEGF-A or both VEGF-A and PDGF-B signaling pathways could be effective for diffuse-type gastric carcinomas.

Place, publisher, year, edition, pages
2010. Vol. 10, 659- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-139241DOI: 10.1186/1471-2407-10-659ISI: 000285689800001PubMedID: 21118571OAI: oai:DiVA.org:uu-139241DiVA: diva2:380893
Available from: 2010-12-22 Created: 2010-12-22 Last updated: 2011-02-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
BMC Cancer
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 171 hits
ReferencesLink to record
Permanent link

Direct link