title: Periostin: a putative mediator involved in tumour resistance to anti-angiogenic therapy?
abstract: Despite advances in the development of anti-angiogenic agents for cancer treatment, the increase in the survival duration of cancer patients is still rather modest. One major obstacle in anti-angiogenic therapy is the emergence of drug resistance. Understanding the molecular mechanisms that enable a tumour to evade anti-angiogenic treatment is valuable to improve therapeutic efficacy. Targeting blood supply usually causes hypoxic responses of tumours that trigger a series of adaptive changes leading to a resistant phenotype. Periostin, a secreted ECM (extracellular matrix) protein, is mainly produced by CAFs (cancer-associated fibroblasts) on hypoxic stress. As CAFs have been casually linked to tumour resistance to angiogenesis blockade and periostin can influence many aspects of tumour biology, we hypothesized that periostin might be a crucial mediator involved anti-angiogenic resistance in cancer treatment. This hypothesis is indirectly supported by the following facts: (a) high levels of periostin promote tumour angiogenesis; (b) periostin improves cancer cell survival under hypoxic conditions; and (c) genetic modulation of periostin induces EMT (epithelial-mesenchymal transition) and enhances cancer cell invasion and metastasis, which represents an escape mechanism from anticancer treatment. Testing and confirmation of this hypothesis will give more insight into the resistance mechanisms and provide the rationale for improvement of therapeutic outcome of anti-angiogenic therapy.
authors: Center for the Study of Liver Cancer and Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei, Peoples Republic of China. whouwei@sina.com
authors: Wei
authors: W
authors: Wang
authors: Jin-Liang
authors: JL
authors: Ma
authors: Wei-Dong
authors: WD
authors: Jia
authors: Ge-Liang
authors: GL
authors: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000473:pathology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C082838:Postn protein, mouse; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor