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

Kerstin Galler, Kerstin Junker, Marcus Franz, Julia Hentschel, Petra Richter, Mieczyslaw Gajda, Angela Göhlert, Ferdinand Von Eggeling, Regine Heller, Raffaella Giavazzi, Dario Neri, Hartwig Kosmehl, Heiko Wunderlich, Alexander Berndt

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)195-204
Number of pages10
JournalHistochemistry and Cell Biology
Volume137
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Keywords

  • Angiogenesis
  • Antibody-based pharmacodelivery
  • Fibronectin
  • Renal cell carcinoma
  • Tenascin-C

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Medical Laboratory Technology
  • Molecular Biology

Cite this

Galler, K., Junker, K., Franz, M., Hentschel, J., Richter, P., Gajda, M., Göhlert, A., Von Eggeling, F., Heller, R., Giavazzi, R., Neri, D., Kosmehl, H., Wunderlich, H., & Berndt, A. (2012). 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. Histochemistry and Cell Biology, 137(2), 195-204. https://doi.org/10.1007/s00418-011-0886-z