Cao, Yihai - Karolinska Institute - Department of Microbiology, Tumor and Cell Biology

研究领域

Studies of pro-angiogenic factors We are studying the molecular mechanisms of angiogenesis and vascular permeability induced by the family of vascular endothelial growth factor (VEGF) which is overexpressed in virtually all types of tumors. We are characterizing the signal transduction events mediated by the VEGF receptors. We aim to develop VEGF antagonists and agonists that can be used for disease therapy. In addition, we have found that leptin, a hormone produced by fat tissue, induces angiogenesis. We are characterizing the signaling pathways induced by this novel angiogenic factor. Further we are studying the role of angiogenesis in cardiovascular diseases. We are developing methods to use angiogenic factors to establish the alternative circulation pathways after heart attack. This work relates to a recently published project dealing with the stability of the established blood vessels. Studies of anti-angiogenic factors We are searching for potent angiogenesis inhibitors that can be used in cancer therapy. We are particularly interested in angiostatin and its related molecules that specifically target the newly formed blood vessels and have no effect on the existing vasculature. Previous studies have shown that angiostatin is a potent tumor suppressor. However, the only problem is that the dosage of angiostatin used in animal studies seems to be too high to be realistic in clinical trials. How do we overcome this problem in order to move the laboratory study to the bedside? We have developed several alternative strategies that may allow us to overcome the problem. First, Renhai Cao and Niina Veitomäki have found a more potent molecule than angiostatin, namely kringle 1-5 (ref) of plasminogen that suppresses tumor growth in mice at low dosages. We are studying the molecular mechanisms of this novel angiogenesis inhibitor. We are also developing other therapeutic approaches for targeting the vascular compartment. These approaches include gene therapy, tumor targeting, slow release polymers and combinatorial therapy. In addition, we have identified several new angiogenic and antiangiogenic molecules that can be potentially used for disease therapy. These include VEGF-C (ref), leptin (ref), interleukin-18 (ref) and chemokines. The molecular mechanisms underlying how these inhibitors suppress angiogenesis are being studied. Members in our group often drink green tea instead of coffee during our tea breaks. In fact, there are some good reasons to drink green tea because it contains a compound named epigallocatechin-3-gallate (EGCG), which has been reported to suppress the growth of a variety types of tumors in animals. We have recently found that drinking green tea suppresses angiogenesis in animal models (ref). Thus, drinking green tea may become beneficial not only for cancer prevention but also for prevention of other angiogenic diseases such as diabetes. We recommend you to begin drinking green tea for the benefit of your own health. You can contact Renhai for receiving samples of green tea. Antiangiogenesis We run several rigorous angiogenesis assays including the chick chorioallantoic membrane assay, the mouse corneal micropocket assay, the endothelial cell growth (proliferation) assay, the endothelial motility assay and the tumor angiogenesis assay. If you have some molecules that may be involved in regulation of angiogenesis, you are welcome to contact Dr. Yihai Cao.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Pericyte-fibroblast transition promotes tumor growth and metastasis. Hosaka K, Yang Y, Seki T, Fischer C, Dubey O, Fredlund E, et al. Proc. Natl. Acad. Sci. U.S.A. 2016 Sep;113(38):E5618-27 Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism. Yang Y, Zhang Y, Iwamoto H, Hosaka K, Seki T, Andersson P, et al. Nat Commun 2016 Sep;7():12680 Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat. Seki T, Hosaka K, Lim S, Fischer C, Honek J, Yang Y, et al. Nat Commun 2016 Aug;7():12152 Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism. Jia M, Andreassen T, Jensen L, Bathen T, Sinha I, Gao H, et al. Cancer Res. 2016 Oct;76(19):5634-5646 Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis. Lim S, Hosaka K, Nakamura M, Cao Y. Oncotarget 2016 Jun;7(25):38282-38291 The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages. Yang Y, Andersson P, Hosaka K, Zhang Y, Cao R, Iwamoto H, et al. Nat Commun 2016 May;7():11385 Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy. Zhang Y, Yang Y, Hosaka K, Huang G, Zang J, Chen F, et al. Proc. Natl. Acad. Sci. U.S.A. 2016 Apr;113(15):4158-63 Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE. Carmona G, Perera U, Gillett C, Naba A, Law A, Sharma V, et al. Oncogene 2016 Sep;35(39):5155-69 MT1-MMP sheds LYVE-1 on lymphatic endothelial cells and suppresses VEGF-C production to inhibit lymphangiogenesis. Wong H, Jin G, Cao R, Zhang S, Cao Y, Zhou Z. Nat Commun 2016 Mar;7():10824 Future options of anti-angiogenic cancer therapy. Cao Y. Chin J Cancer 2016 Feb;35():21 Resveratrol analogue 4,4'-dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis. Savio M, Ferraro D, Maccario C, Vaccarone R, Jensen L, Corana F, et al. Sci Rep 2016 Feb;6():19973 VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish. Jensen L, Nakamura M, Bräutigam L, Li X, Liu Y, Samani N, et al. Proc. Natl. Acad. Sci. U.S.A. 2015 Nov;112(44):E5944-53 Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain. Hameed L, Berg D, Belnoue L, Jensen L, Cao Y, Simon A. Elife 2015 Oct;4(): Invasiveness and metastasis of retinoblastoma in an orthotopic zebrafish tumor model. Chen X, Wang J, Cao Z, Hosaka K, Jensen L, Yang H, et al. Sci Rep 2015 Jul;5():10351 VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients. Yang X, Zhang Y, Hosaka K, Andersson P, Wang J, Tholander F, et al. Proc. Natl. Acad. Sci. U.S.A. 2015 Jun;112(22):E2900-9 CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer. Svensson S, Abrahamsson A, Rodriguez G, Olsson A, Jensen L, Cao Y, et al. Clin. Cancer Res. 2015 Aug;21(16):3794-805 PlGF-induced VEGFR1-dependent vascular remodeling determines opposing antitumor effects and drug resistance to Dll4-Notch inhibitors. Hideki Iwamoto, Yin Zhang, Takahiro Seki, Yunlong Yang, Masaki Nakamura, Jian Wang, Xiaojuan Yang, Takuji Torimura, Yihai Cao. Science Advances 10 Apr 2015: Vol. 1 no. 3 e1400244 DOI: 10.1126/sciadv.1400244 MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes. Keklikoglou I, Hosaka K, Bender C, Bott A, Koerner C, Mitra D, et al. Oncogene 2015 Sep;34(37):4867-78 Hypoxic regulation of RIOK3 is a major mechanism for cancer cell invasion and metastasis. Singleton D, Rouhi P, Zois C, Haider S, Li J, Kessler B, et al. Oncogene 2015 Sep;34(36):4713-22 Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development. Wang J, Cao Z, Zhang X, Nakamura M, Sun M, Hartman J, et al. Cancer Res. 2015 Jan;75(2):306-15 VEGFR2-mediated vascular dilation as a mechanism of VEGF-induced anemia and bone marrow cell mobilization. Lim S, Zhang Y, Zhang D, Chen F, Hosaka K, Feng N, et al. Cell Rep 2014 Oct;9(2):569-80 Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues. Honek J, Seki T, Iwamoto H, Fischer C, Li J, Lim S, et al. Proc. Natl. Acad. Sci. U.S.A. 2014 Oct;111(41):14906-11 Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration. He C, Zhao C, Kumar A, Lee C, Chen M, Huang L, et al. Proc. Natl. Acad. Sci. U.S.A. 2014 Oct;111(41):14806-11 TNFR1 mediates TNF-α-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Ji H, Cao R, Yang Y, Zhang Y, Iwamoto H, Lim S, et al. Nat Commun 2014 Sep;5():4944 VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs. Cao Y. Nat Rev Endocrinol 2014 Sep;10(9):530-9 Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer. Zhao C, Qiao Y, Jonsson P, Wang J, Xu L, Rouhi P, et al. Cancer Res. 2014 Jul;74(14):3983-94 Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response. Zheng X, Zhou A, Rouhi P, Uramoto H, Borén J, Cao Y, et al. Proc. Natl. Acad. Sci. U.S.A. 2014 Feb;111(7):2560-5 Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis. Arjonen A, Kaukonen R, Mattila E, Rouhi P, Högnäs G, Sihto H, et al. J. Clin. Invest. 2014 Mar;124(3):1069-82