Establishment of red fluorescent protein-tagged HeLa tumor metastasis models: determination of DsRed2 insertion effects and comparison of metastatic patterns after subcutaneous, intraperitoneal, or intravenous injection.
Metastasis is the leading cause of death in patients with cervical cancer. In this report, we establish novel fluorescent HeLa tumor metastasis models to determine whether HeLa transfected with the enhanced red fluorescent protein (DsRed2) gene in vitro and xenotransplanted through subcutaneous, intraperitoneal, or intravenous route into SCID mice would permit the detection of tumor micro-metastasis in vivo. Our results showed that DsRed2 insertions did not interfere the tumorigenic properties of HeLa cells. We also demonstrated that DsRed2-transduced HeLa cells maintained stable high-level DsRed2 expressions during their growth in vivo. DsRed2 fluorescence clearly demarcated the primary seeding place and readily allowed for the visualization of distant micro-metastasis and local invasion at the single-cell level. Lung metastasis, the major cause of cervical carcinoma related death, was found in all three models. However, intravenous injections of the HeLa-DsRed2 cells established tumor foci in the lung, while subcutaneous and intraperitoneal injections only established lung metastasis at single-cell levels. The DsRed2 tagged HeLa cancer model allowed detection and investigation of physiologically relevant patterns of cancer invasion and metastasis in vivo.
Lu
Jau-Yeong
JY
Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Chen
Hui-Chun
HC
Chu
Ricky Yuan-Yuan
RY
Lin
Tsu-Chun Emma
TC
Hsu
Ping-I
PI
Huang
Ming-Shyan
MS
Tseng
Ching-Jiunn
CJ
Hsiao
Michael
M
D000818:Animals; D002455:Cell Division; D003114:Colony-Forming Units Assay; D005260:Female; D006367:HeLa Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008164:Luminescent Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014162:Transfection; D014183:Transplantation, Heterologous; D000097573:Red Fluorescent Protein
D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein