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PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer.

ABSTRACT: Unlike platelet-derived growth factor-B (PDGF-B), the role of PDGF-D in tumor progression or treatment is largely unknown. To this end, we determined the role of PDGF-D in breast cancer progression, metastasis, and response to chemotherapy.We first examined PDGF-D expression in human breast carcinomas by immunohistochemical (IHC) staining. To mimic high PDGF-D expressing tumors, we stably transfected the breast cancer cell lines MDA-MB-231 and 4T1 with pdgf-d cDNA, and implanted these tumor cells orthtopically into nude mice. We monitored tumor growth by caliper measurement and bioluminescence imaging. We also used short hairpin RNA interference (shRNAi) and imatinib to block PDGF-D/PDGFR? signaling. Finally, we studied the effect of PDGF-D on doxorubicin delivery and efficacy.Human breast cancers express high levels of PDGF-D. Overexpression of PDGF-D promoted tumor growth and lymph node metastasis through increased proliferation, decreased apoptosis, and induction of CXCR4 expression. Blockade of CXCR4 signaling abolished PDGF-D-induced lymph node metastasis. Furthermore, overexpression of PDGF-D increased perivascular cell coverage and normalized tumor blood vessels. As a result, PDGF-D overexpression facilitated tissue penetration of doxorubicin and enhanced its treatment efficacy.PDGF-D is highly expressed in human breast cancer and facilitates tumor growth and lymph node metastasis, making it a potential target in breast cancer. At the same time, PDGF-D increases drug delivery and hence improves the efficacy of chemotherapy through vessel normalization. Therefore, judicious use of PDGF-D/PDGFR? blockers would be necessary to minimize the adverse effects on concomitantly administered cytotoxic therapies.

SUBMITTER: Liu J

PROVIDER: S-EPMC3107920 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer.

Liu Jieqiong J Liao Shan S Huang Yuhui Y Samuel Rekha R Shi Tony T Naxerova Kamila K Huang Peigen P Kamoun Walid W Jain Rakesh K RK Fukumura Dai D Xu Lei L

Clinical cancer research : an official journal of the American Association for Cancer Research 20110401 11

<h4>Purpose</h4>Unlike platelet-derived growth factor-B (PDGF-B), the role of PDGF-D in tumor progression or treatment is largely unknown. To this end, we determined the role of PDGF-D in breast cancer progression, metastasis, and response to chemotherapy.<h4>Experimental design</h4>We first examined PDGF-D expression in human breast carcinomas by immunohistochemical (IHC) staining. To mimic high PDGF-D expressing tumors, we stably transfected the breast cancer cell lines MDA-MB-231 and 4T1 with ...[more]

PMID: 21459800

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Dataset Information

PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer.

Publications

PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer.

Similar Datasets

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