ED-B FIBRONECTIN IN NON–SMALL CELL LUNG CARCINOMA

Abstract

Fibronectin (FN), a matrix glycoprotein, has been shown to undergo alternative splicing exclusively during organogenesis and tumorigenesis. One such splice variant, extradomain-B (ED-B) FN, is normally absent in normal adult tissues and is proposed to be a marker of tumoral angiogenesis. The present study was aimed at elucidating whether ED-B FN is expressed in non–small cell lung carcinomas and whether such aberrant expression correlates with tumoral angiogenesis. Frozen tissues from 28 non–small cell lung carcinomas (consisting of both squamous cell carcinomas and adenocarcinomas) along with paired normal tissue samples were collected from the tissue bank collection of the Department of Pathology, London Health Sciences Center, Canada. Frozen tissue specimens were subjected to RNA extraction and real time reverse transcriptase–polymerase chain reaction (RT-PCR) with respect to total and ED-B FN isoform expression. In addition, paraffin-embedded tissue sections from the same cases were collected for histological analysis using ED-B FN antibody. Tumor tissues were further stained with CD34 antibody and analyzed semiquantitatively for tumor microvessel density. The results demonstrate up-regulation of ED-B FN mRNA levels in lung tumor tissues as compared to paired normal tissues. Furthermore, ED-B FN expression was localized specifically to tumor cells and was found to correlate with tumor microvessel density. These findings provide evidence of possible involvement of ED-B FN in pulmonary tumoral angiogenesis. Furthermore, ED-B FN may potentially be used as a diagnostic marker and a target for antiangiogenic therapy.

Keywords:

• angiogenesis
• cancer
• ED-B
• extracellular matrix
• lung

Additional information

Notes on contributors

Zia A. Khan

The current address of Zia A. Khan is Vascular Biology Research Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.