title: Increased lymphatic vascular density is seen before colorectal cancers reach stage II and growth factor FGF-2 is downregulated in tumor tissue compared with normal mucosa.
abstract: Lymphangiogenesis is an important event in progression of colorectal cancer (CRC), and the estimated lymphatic vascular density (LVD) probably indicates facilitated lymphatic tumor cell invasion and metastasis. However, at what time point during tumor progression this process is triggered, is unclear. The aim of this study was twofold. Firstly, to examine LVD in paired samples of CRC tissue and normal mucosa with specific emphasis on possible difference in LVD between tumors stages II and III, and secondly, the expression of the lymphangiogenic growth factor fibroblast growth factor-2 (FGF-2). Eighteen patients were studied. Immunostaining for podoplanin was performed to highlight lymphatic vessels. FGF-2 mRNA expression was determined by quantitative real-time RT-PCR, whereas protein expression was quantitatively assessed by densitometric analysis of Western blot signal intensity. The immunoblots were further validated by FGF-2 immunostaining of histological sections. LVD was significantly increased in tumor tissue compared with the normal mucosa but no changes in LVD between stages II and III CRC was observed. FGF-2 was found to be downregulated both at the mRNA and protein level in tumor tissues compared with normal mucosa. Lymphangiogenesis was triggered early in tumor development. An increased LVD was established before the tumor reached stage II. FGF-2 was downregulated in tumor tissue. The importance of this finding remains unclear.
authors.affiliation: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen, Norway. eirik.sundlisater@biomed.uib.no
authors.forename: Eirik
authors.initials: E
authors.lastname: Sundlisaeter
authors.forename: Gro Vatne
authors.initials: GV
authors.lastname: Røsland
authors.forename: Jens Kristoffer
authors.initials: JK
authors.lastname: Hertel
authors.forename: Per Øystein
authors.initials: PØ
authors.lastname: Sakariassen
authors.forename: Bjarte
authors.initials: B
authors.lastname: Almås
authors.forename: Aly
authors.initials: A
authors.lastname: Dicko
authors.forename: Karl
authors.initials: K
authors.lastname: Søndenaa
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2