Role of bFGF and HGF in colon adenocarcinoma growth in liver

Introduction: Basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) are important positive regulators of tumor growth and angiogenesis. This study was designed to assess the effect of bFGF and HGF infusion on tumor growth and metastases in a syngeneic, rat colon adenocarcinoma tumor model. Methods: Liver tumors were established in each of 21 BD9 rats via surgical, subcapsular implantation of a 1.0 mm3 piece of a subcutaneously grown DHD/K12/TRb tumor. Test groups were infused systemically with 5 μg/day/rat bFGF or 0.5 μg/day/rat HGF via osmotic pump; and controls received saline. At 28 days all animals were killed and examined. Tumor volume was calculated as π[a2 × b]/6, where a is shorter length and b the longer length. Liver and lung specimens were fixed in zinc formalin and embedded in paraffin for H&E staining and immunohistochemical study. Results: On histologic examination, tumor cells were seen to grow along blood vessel branches after infusion bFGF and HGF. Both VEGF and Flk-1 expression was strong cytoplasmic staining in cancer cells from hepatic, peritoneal and lung metastases. Conclusion: While both bFGF and HGF appear to induce an increase in tumor growth in this model, the effect of bFGF was marked. Similarly, HGF appeared to stimulate the development of distant metastases, though not reaching significance, while bFGF produced local and distant metastases with statistically significant increase in lung metastases. This rat colon adenocarcinoma cell line expressed VEGF and its receptor Flk-1. Further studies are required to evaluate the mechanism of tumor growth and metastasis stimulation. <TBL LOC="DISPLAY"><NO>TABLE—ABSTRACT P8</NO><TBLBDY TOP-STUBS="1" LEFT-STUBS="0" BOTTOM-STUBS="0" RIGHT-STUBS="0"><R><C CSPAN="1" RSPAN="1" CA="C" RA="B"><TOP-BORDER TYPE="BAR" STYLE="S"><BOTTOM-BORDER TYPE="BAR" STYLE="S"></C><C CSPAN="1" RSPAN="1" CA="C" RA="B"><TOP-BORDER TYPE="BAR" STYLE="S"><BOTTOM-BORDER TYPE="BAR" STYLE="S">Control (n = 7)</C><C CSPAN="1" RSPAN="1" CA="C" RA="B"><TOP-BORDER TYPE="BAR" STYLE="S"><BOTTOM-BORDER TYPE="BAR" STYLE="S">bFGF (n = 7)</C><C CSPAN="1" RSPAN="1" CA="C" RA="B"><TOP-BORDER TYPE="BAR" STYLE="S"><BOTTOM-BORDER TYPE="BAR" STYLE="S">HGF (n = 6&ast;)</C><C CSPAN="1" RSPAN="1" CA="C" RA="B"><TOP-BORDER TYPE="BAR" STYLE="S"><BOTTOM-BORDER TYPE="BAR" STYLE="S">P value</C></R><R><C CSPAN="1" RSPAN="1" CA="L" RA="T">Tumor volume (mm3)</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">48.8 ± 17.6</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">85.1 ± 25.0†</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">59.3 ± 26.9</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">†<.05</C></R><R><C CSPAN="1" RSPAN="1" CA="L" RA="T">Intrahepatic mets</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">0</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">3/7‡</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">0</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">‡=.19</C></R><R><C CSPAN="1" RSPAN="1" CA="L" RA="T">Peritoneal mets</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">0</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">3/7‡</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">1/6</C><C CSPAN="1" RSPAN="1" CA="C" RA="T">‡=.19</C></R><R><C CSPAN="1" RSPAN="1" CA="L" RA="T"><BOTTOM-BORDER TYPE="BAR" STYLE="S">Lung mets&ast;&ast;</C><C CSPAN="1" RSPAN="1" CA="C" RA="T"><BOTTOM-BORDER TYPE="BAR" STYLE="S">0</C><C CSPAN="1" RSPAN="1" CA="C" RA="T"><BOTTOM-BORDER TYPE="BAR" STYLE="S">5/7‡</C><C CSPAN="1" RSPAN="1" CA="C" RA="T"><BOTTOM-BORDER TYPE="BAR" STYLE="S">1/6</C><C CSPAN="1" RSPAN="1" CA="C" RA="T"><BOTTOM-BORDER TYPE="BAR" STYLE="S">‡=.02</C></R></TBLBDY><TBLFN ID="TBLFN1"><NO>&ast;</NO>One rat in this group died at postoperative two weeks.</TBLFN><TBLFN ID="TBLFN2"><NO>†,‡</NO>bFGF group vs control group by Kruskal Wallis test.</TBLFN></TBL> [Copyright &y& Elsevier]