Selective suppression of metastasis but not tumorigenicity of a mouse lung carcinoma by cell hybridization
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Abstract:
Somatic cell hybrids were produced by polyethylene glycol-induced cell fusion between metastatic CMT 167 (HGPRT-/OUAR) C57BL/Icrfat mouse lung carcinoma cells and 2 non-metastatic cell lines: C3H/He mouse L-M(TK-) cells of mesenchymal origin and EJ (OUAS) human bladder carcinoma cells. Fusion of 2 different CMT167 (HGPRT-) clones with L-M(TK-) cells followed by selection in HMT medium gave rise to 14 intraspecific hybrids, which were shown to express H-2 antigens specific for both the C57 and C3H mouse strains. Three interspecific hybrids arising from fusion of EJ(OUAS) and CMT167(HGPRT-/OUAR) cells were selected in HMT/ouabain medium and characterized by human isozyme analysis. All the hybrids produced large tumours after subcutaneous inoculation of 5 X 10(5) cells into adult athymic nu/nu mice. The intraspecific hybrid tumours were predominantly sarcomatous (mesenchymal) in structure but a few contained epithelial acini. Metastatic ability (as assessed by production of lung metastases) was completely suppressed in 13 of the 14 mouse/mouse hybrid cell clones. These results suggest that tumorigenicity, tumour structure and the ability to metastasize are expressed independently. The interspecific hybrids, which had not retained a full human chromosome complement, produced metastatic tumours that remained epithelial in structure.
Insights
Creating somatic cell hybrids revealed that tumorigenicity, tumor structure, and metastasis are independent traits. Suppressing metastasis in mouse hybrids suggests distinct genetic controls for these cancer characteristics.
Area of Science:
- Cancer Biology
- Cell Fusion
- Tumorigenesis
Background:
- Metastatic cancer remains a significant challenge in oncology.
- Understanding the genetic basis of metastasis is crucial for developing effective therapies.
- Somatic cell hybridization offers a method to study gene regulation in cancer progression.
Purpose of the Study:
- To investigate the independent regulation of tumorigenicity, tumor structure, and metastatic potential.
- To generate and characterize somatic cell hybrids between metastatic and non-metastatic cell lines.
- To explore the genetic control mechanisms underlying cancer cell behavior.
Main Methods:
- Polyethylene glycol-induced cell fusion of mouse lung carcinoma cells (CMT 167) with mouse mesenchymal cells (L-M(TK-)) and human bladder carcinoma cells (EJ).
- Selection of intraspecific (mouse/mouse) and interspecific (mouse/human) hybrids using specific culture media (HMT, HMT/ouabain).
- Characterization of hybrids through H-2 antigen expression, human isozyme analysis, and tumor formation/metastasis assays in athymic mice.
Main Results:
- Fourteen intraspecific hybrids expressed parental H-2 antigens. Three interspecific hybrids were identified via human isozyme analysis.
- All hybrids formed tumors in vivo. Intraspecific hybrid tumors were primarily sarcomatous, with some epithelial components.
- Metastasis was suppressed in 13 out of 14 intraspecific hybrids. Interspecific hybrids produced metastatic, epithelial tumors.
Conclusions:
- Tumorigenicity, tumor structure, and metastatic ability appear to be independently regulated traits.
- Suppression of metastasis in intraspecific hybrids suggests distinct genetic control mechanisms.
- Interspecific hybrids, lacking full human chromosome complements, retained metastatic potential and epithelial structure.