title: High interstitial fluid pressure in rat tongue cancer is related to increased lymph vessel area, tumor size, invasiveness and decreased body weight.
abstract: BACKGROUND
  Interstitial fluid pressure (IFP) in most tumors is high, and this high pressure has been correlated with poor prognosis. Measurements of IFP in normal tongue and in tongue cancer are lacking. Recent research suggests the existence of a relationship between increased peritumoral lymph vessels (PTLV) and survival, and a correlation of increased lymphatic vessel density with an unfavorable prognosis has been reported.
  
  
  METHODS
  In the present study, tongue squamous cell carcinoma (SCC) was induced by adding the carcinogen 4-nitroquinoline oxide in drinking water for 19 weeks. The IFP was measured by micropuncture and immunohistochemistry was used to visualize lymph vessels.
  
  
  RESULTS
  In normal tongue, IFP averaged 3.1 +/- 0.3 mmHg. The IFP, both in the tumor (29.1 +/- 2.9 mmHg) and 0.5 cm anterior to it (15.4 +/- 2.1 mmHg) was consistently increased (P < 0.005) with values ranging from 10 to 40 mmHg. The highest IFP values were measured in rats with large tumors (P < 0.05) and low body weight (P < 0.001), suggesting that IFP increases with cancer progression. Lymphatic vessel area (%), as determined with the lymphatic specific marker LYVE-1 antibody, was significantly increased in the peritumoral area when compared to intratumoral and control mucosa (P < 0.05). There was a significant positive correlation between IFP, PTLV area, tumor size and invasiveness.
  
  
  CONCLUSIONS
  Our data show that IFP is increased in tongue cancer. Corresponding changes in PTLV area, invasiveness, tumor area and IFP suggest that the increased pressure is caused by defective lymph drainage and solid stress generated by tumor cells growing in a low compliant environment.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway. bina.raju@biomed.uib.no
authors.forename: Bina
authors.initials: B
authors.lastname: Raju
authors.forename: Sivakami Rethnam
authors.initials: SR
authors.lastname: Haug
authors.forename: Salah Osman
authors.initials: SO
authors.lastname: Ibrahim
authors.forename: Karin Johanne
authors.initials: KJ
authors.lastname: Heyeraas
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D045604:Extracellular Fluid / Q000502:physiology*; D042601:Lymphatic Vessels / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009361:Neoplasm Invasiveness; D011312:Pressure; D015363:Quinolones; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
chemical_list: C120195:4-nitroquinolone-1-oxide; D015363:Quinolones; D015112:4-Nitroquinoline-1-oxide