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: 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
• Journal: Histochemistry and cell biology (Histochem Cell Biol) Vol. 137 Issue 2 Pg. 195-204 (Feb 2012) ISSN: 1432-119X [Electronic] Germany
• PMID: 22075565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibronectins
• Protein Isoforms
• RNA, Messenger
• Tenascin
• Vascular Endothelial Growth Factor A

Topics

• Adenocarcinoma, Clear Cell (blood supply, pathology, secondary)
• Animals
• Blood Vessels (metabolism, pathology)
• Carcinoma, Papillary (blood supply, pathology, secondary)
• Carcinoma, Renal Cell (blood supply, pathology, secondary)
• Female
• Fibronectins (metabolism)
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Kidney Neoplasms (blood supply, pathology, secondary)
• Mice
• Mice, Nude
• Neovascularization, Pathologic
• Protein Isoforms (metabolism)
• RNA, Messenger (metabolism)
• Tenascin (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)