BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors
| العنوان: | BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors |
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| المؤلفون: | Masabumi Shibuya, Masashi Muramatsu, S Tsuchida, Takashi Takahashi, Takafumi Inoue, F Wang, R Nishii, Takashi Minami, Youichiro Wada, Rika Tsuchida, Bikul Das, Tsuyoshi Osawa, Yasuhito Yuasa |
| المصدر: | Oncogene. 33:3803-3811 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Smad5 Protein, Cancer Research, animal structures, Angiogenesis, Melanoma, Experimental, Bone Morphogenetic Protein 4, Biology, Vascular endothelial growth inhibitor, Smad1 Protein, Thrombospondin 1, Mice, chemistry.chemical_compound, Cancer stem cell, Cell Line, Tumor, Neoplasms, Paracrine Communication, Genetics, Animals, Humans, Molecular Biology, Cell Proliferation, Tumor microenvironment, Neovascularization, Pathologic, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Endothelial Cells, Tumor Burden, Vascular endothelial growth factor, HIF1A, chemistry, embryonic structures, Immunology, Cancer cell, Cancer research, HeLa Cells, Signal Transduction |
| الوصف: | Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1670ea0a088f0c4b773dde1b92bf3caeTest https://doi.org/10.1038/onc.2013.358Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1670ea0a088f0c4b773dde1b92bf3cae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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