title: Metastasis-associated in colon cancer-1 upregulates vascular endothelial growth factor-C/D to promote lymphangiogenesis in human gastric cancer.
abstract: Lymphangiogenesis is actively contributed to lymphatic metastasis in gastric cancer (GC), and vascular endothelial growth factor (VEGF)-C and VEGF-D are key regulators for lymphangiogenesis. Metastasis-associated in colon cancer-1 (MACC1) was reported to be associated with lymph node metastasis in a few clinical studies, while little is known about the role of MACC1 in lymphangiogenesis. Hence, in the present study, we explored the potential role of MACC1 in lymphangiogenesis as well as the underlying mechanisms. By clinical observation, we found a positive relationship between MACC1 and lymphangiogenesis. Besides, similar results were also obtained from in vivo and in vitro studies. With an indirect co-culture system, we got that supernatant from MACC1 overexpressed GC cells accelerated human lymphatic endothelial cells' (HLECs') capacity of tube-like formation through enhancing cell proliferation and migration. Moreover, MACC1 overexpressed xenografts also presented more lymphatic vessels. Furthermore, MACC1 significantly increased the expression of VEGF-C/VEGF-D in GC cells and transplanted tumors, which was subsequently suppressed by c-Met inhibitor. All these data suggested a critical role for MACC1 in lymphatic dissemination of GC, providing evidence that MACC1 upregulated VEGF-C/VEGF-D secretion to promote lymphangiogenesis via c-Met signaling.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jiangman
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Oncology, Subei People's Hospital, Yangzhou University, Yangzhou 225001, China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Cardiology and Organ Failure Key Laboratory of Ministry of Education, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: nfyyliaowj@163.com.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D042583:Lymphangiogenesis / Q000502:physiology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C544162:MACC1 protein, human; C575027:MACC1 protein, mouse; D009363:Neoplasm Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D
keywords: Gastric cancer; Lymphangiogenesis; Metastasis-associated in colon cancer-1; Vascular endothelial growth factor-C/D; c-Met signaling