title: Differential vascular expression and regulation of oncofetal tenascin-C and fibronectin variants in renal cell carcinoma (RCC): implications for an individualized angiogenesis-related targeted drug delivery.
abstract: The study was aimed at determining the vascular expression of oncofetal fibronectin (oncfFn) and tenascin-C (oncfTn-C) isoforms in renal cell carcinoma (RCC) and its metastases which are well-known targets for antibody-based pharmacodelivery. Furthermore, the influence of tumour cells on endothelial mRNA expression of these molecules was investigated. Evaluation of vascular ED-A(+) and ED-B(+) Fn as well as A1(+) and C(+) Tn-C was performed after immunofluorescence double and triple staining using human recombinant antibodies on clear cell, papillary and chromophobe primary RCC and metastases. The influence of hypoxic RCC-conditioned medium on oncfFn and oncfTn-C mRNA expression was examined in human umbilical vein endothelial cells (HUVEC) by real time RT-PCR. There are RCC subtype specific expression profiles of vascular oncfFn and oncfTn-C and corresponding patterns when comparing primary tumours and metastases. Within one tumour, there are different vessel populations with regard to the incorporation of oncfTn-C and oncfFn into the vessel wall. In vitro tumour-derived soluble mediators induce an up regulation of oncfTn-C and oncfFn mRNA in HUVEC which can be blocked by Avastin(®). Vascular expression of oncFn and oncTn-C variants depends on RCC subtype and may reflect an individual tumour stroma interaction or different stages of vessel development. Therefore, oncFn or oncTn-C variants can be suggested as molecular targets for individualized antibody based therapy strategies in RCC. Tumour-derived VEGF could be shown to regulate target expression.
authors.affiliation: Institute of Pathology, University Hospital Jena, Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Galler
authors.forename: Kerstin
authors.initials: K
authors.lastname: Junker
authors.forename: Marcus
authors.initials: M
authors.lastname: Franz
authors.forename: Julia
authors.initials: J
authors.lastname: Hentschel
authors.forename: Petra
authors.initials: P
authors.lastname: Richter
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Angela
authors.initials: A
authors.lastname: Göhlert
authors.forename: Ferdinand
authors.initials: F
authors.lastname: von Eggeling
authors.forename: Regine
authors.initials: R
authors.lastname: Heller
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giavazzi
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Hartwig
authors.initials: H
authors.lastname: Kosmehl
authors.forename: Heiko
authors.initials: H
authors.lastname: Wunderlich
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000098:blood supply / Q000473:pathology / Q000556:secondary; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000098:blood supply / Q000473:pathology / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D005353:Fibronectins; D020033:Protein Isoforms; D012333:RNA, Messenger; D019063:Tenascin; D042461:Vascular Endothelial Growth Factor A
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