The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells

Abstract

Flt-4, a VEGF receptor, is activated by its specific ligand, VEGF-C. The resultant signaling pathway promotes angiogenesis and/or lymphangiogenesis. This report provides evidence that the VEGF-C/Flt-4 axis enhances cancer cell mobility and invasiveness and contributes to the promotion of cancer cell metastasis. VEGF-C/Flt-4-mediated invasion and metastasis of cancer cells were found to require upregulation of the neural cell adhesion molecule contactin-1 through activation of the Src-p38 MAPK-C/EBP-dependent pathway. Examination of tumor tissues from various types of cancers revealed high levels of Flt-4 and VEGF-C expression that correlated closely with clinical metastasis and patient survival. The VEGF-C/Flt-4 axis, through upregulation of contactin-1, may regulate the invasive capacity in different types of cancer cells.

Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol

“…Cell cultures were maintained at 37°C in a humidified 5% CO 2 atmosphere. For the cell cycle analysis, proliferating cells were serum-starved for 24 h and then treated with vehicle or resveratrol for 24 h. Cells were then subjected to flow cytometric analysis as described previously (19).…”

“…Immunoprecipitation and Western Blot Analysis-Protein expression was detected by Western blot analysis as described previously (19). Equal amounts of protein were incubated with specific antibody immobilized onto protein A-Sepharose for 2 h at 4°C with gentle rotation.…”

“…Anchorage-independent Growth Assay-Colony-forming assays in soft agarose were performed as described previously (19). Cells were seeded in 6-well culture dishes in suspensions of 0.35% Agar noble in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum on top of a bed of 0.7% Agar noble in the same complete medium.…”

Nuclear expression of Twist promotes lymphatic metastasis in esophageal squamous cell carcinoma

“…13,14 VEGF-C plays significant roles in cancer cell mobility and invasiveness by binding to its receptors. 15,16 Therefore, VEGF-C promotes lymphangiogenesis and, in turn, increases lymphatic metastasis in different cancer types including ESCC. [17][18][19][20][21][22][23] Although the level of Twist was positively correlated with VEGF-C in supraglottic carcinoma, 24 the mechanisms by which Twist and VEGF-C are involved in lymphatic metastasis in ESCC require to be further study.…”

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

“…В совокупности эти данные подкрепляют представление о ключевой роли VEGF-C в формировании лимфатической микрососудистой сети, посредством которой осуществляется метастазирование при РШМ. Важно также отметить, что VEGF-C может выступать в качестве аутокринного фактора [16,17], стимулируя в клетках РШМ те же процессы, что и в клетках эндотелия: реорганизацию цитоскелета, усиление экспрессии медиаторов адгезии, и вследствие этого, повышение подвижности опухолевых клеток и способности к инвазии. Действительно, с помощью иммуногистохимического метода и гибридизации in situ было показано, что по мере прогрессии РШМ в опухолевых клетках усиливается экспрессия VEGFR3, основным лигандом которого является VEGF-C [14,17,18].…”