title: MIA-dependent angiogenesis and lymphangiogenesis are closely associated with progression, nodal metastasis and poor prognosis in tongue squamous cell carcinoma.
abstract: We examined the role of angiogenesis/lymphangiogenesis and the relationship between melanoma inhibitory activity (MIA) and angiogenesis or lymphangiogenesis in oral squamous cell carcinoma (OSCC). One hundred and one formalin-fixed, paraffin-embedded specimens of primary OSCC were evaluated for microvessel density (MVD), lymphovessel density (LVD), expression of vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D and MIA. Fresh frozen 18 samples of primary OSCC were further examined for the expression of VEGF, VEGF-C, VEGF-D and MIA protein by enzyme-linked immunosorbent assay (ELISA). In in vitro analysis, we studied the change of VEGF, VEGF-C and VEGF-D expression after MIA siRNA treatment. Higher MVD, LVD and VEGF expression levels were closely associated with tumour progression, nodal metastasis and poor prognosis. Expression levels of VEGF-C and VEGF-D were only related with nodal metastasis. MIA expression was significantly associated with MVD, LVD, VEGF, VEGF-C and VEGF-D expression by immunohistochemistry and ELISA assay. VEGF, VEGF-C, VEGF-D and MIA expression levels of metastatic tongue cancer HSC-3 cells were higher than those with no metastatic HSC-4 cells, and VEGF, VEGF-C and VEGF-D expression levels were decreased by MIA siRNA treatment in both cells. MIA-dependent angiogenesis/lymphangiogenesis might be a useful therapeutic target in progressive and metastatic OSCC.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.forename: Miyako
authors.initials: M
authors.lastname: Kurihara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Anja Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000502:physiology; D008207:Lymphatic Metastasis; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D042442:Vascular Endothelial Growth Factors