Recapitulating orthotopic tumor model through establishment of a parotid gland tumor with lung metastasis using HeLa cell injection into nude mice.
The interaction between tumor cells and surrounding normal cells is very important in the prognosis of tumors. The object of this study was to determine the effect of recipient bed of tumor xenograft on tumor metastasis using a novel parotid gland tumor model. HeLa cells were xenografted into the parotid gland or subcutaneous tissues of athymic mice. Eight weeks after the transplantation, all mice were euthanized and specimens were immunostained with antibodies for angiogenic factors. FGF-2 was given to HeLa cells and the effect on the cellular migration was determined. EGF was also given to HeLa cells for the evaluation of FGF-2 induction. Immunohistochemical staining was done for the vascular metastasis-related factors on 26 human salivary gland tumors. HeLa cells showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. Immunohistochemical staining revealed overexpression of FGF-2 in the parotid tumors compared to the subcutaneous tumors. The application of FGF-2 to implanting HeLa cells increased the cellular invasion in a dose-dependent manner. The application of EGF increases FGF-2 expression in HeLa cells. In clinical specimens, EGF and VEGF signaling proteins were more expressed than in normal salivary glandular tissues. In conclusion, a parotid tumor model of HeLa cells was successfully developed and it closely mimics high metastasis. These results indicate that recipient bed with intense EGF expression increases tumor metastasis through upregulation of FGF-2 expression.
Park
Young-Wook
YW
Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, Korea.
Kim
Seong-Gon
SG
Choi
Je-Yong
JY
Lee
Suk Keun
SK
D000818:Animals; D003528:Carcinoma, Adenoid Cystic / Q000098:blood supply / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010307:Parotid Neoplasms / Q000098:blood supply / Q000473:pathology*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors