Phenotype alteration in colon carcinoma cells: effect of in vivo passage?

A panel of rat colon adenocarcinoma cell lines (the Per series) were used to investigate the phenotype and karyotype changes induced by in vivo passage in the subcutis of athymic nude mice. One poorly and one well-differentiated tumor cell line were serially passaged through the athymic nude mouse and then back to the syngeneic rat host. Each of the primary and xenograft cell lines expressed fetal crypt cell ("CaCo") antigens. The well differentiated primary and xenograft lines (Per305, Per305N1, and Per305N2a) were different in each of their growth factor responsiveness in vitro [i.e. epidermal growth factor (EGF), bombesin, vasoactive intestinal peptide], their EGF receptor expression, their secretion of transforming growth factor-alpha, and their exhibition of anchorage independent (A-I) growth capabilities. The poorly differentiated primary and xenograft cell lines were also different but were all capable of A-I growth; their responsiveness to exogenous growth factor stimulation decreased with progressive in vivo passage, as did their basal unstimulated proliferation rate. Cytogenetic alterations detected were those associated with clinical specimens from various stages of malignancy, i. e. aneuploidy, structural aberrations, and marker chromosomes. Genetic and mitogenic individuality of each line demonstrated the diversity of the growth control mechanisms in neoplasms at different stages of progression.

Three new rat colon tumour cell lines from 1,2-dimethylhydrazine induced adenocarcinomas: morphology, karyotype and clonogenicity.

Three different tumour cell lines (Per113, Per192, Per237) were established from colon adenocarcinomas induced by 1,2-dimethylhydrazine (DMH) inbred male Wistar/Wag rats. Each cell line had epithelial morphology and an abnormal karyotype. The three cell lines were clonogenic in semi-solid medium, but differed in growth factor response, culture characteristics and karyotype. Each cell line was stimulated differentially by epidermal growth factor (EGF) and bombesin in culture. Only Per192 would passage in vivo in athymic nude mice. Per 113 had modal chromosome number of 70 with multiple structural abnormalities; Per237 had 43 chromosomes with consistent trisomy of chromosome I; 20-25% of the cells in line Per192 were in the tetraploid range with multiple copies of chromosome I.

Single chromosome defect, partial trisomy 1q, in a colon cancer cell line.

The characterization of a single chromosome defect previously reported in a case of inherited nonpolyposis colorectal cancer is the essence of this communication. The defect, originally described as 13p+, is now being defined and the karyotype designated as 46,XY,-13,+der(13)t(1;13)(q32.1;p11).

Four permanent cell lines established from human malignant gliomas: three exhibiting striated muscle differentiation.

Twenty-two human gliomas were set up in tissue culture and inoculated into nude mice. Permanent cell lines were established from four of these and their growth characteristics, and morphological features defined and cytogenetic features described. All four failed to sustain evidence of glial differentiation while three of the four cell lines exhibited the characteristics of striated muscle, and were tumorigenic in nude mice. Nine gliomas showed some initial growth in nude mice but only two were successfully subpassaged.

A chromosome study of three ovarian tumors.

The cytogenetic results of three different types of malignant ovarian tumors are reported. Their chromosomes were studied indirectly by using either peritoneal washings or ascitic fluids. Detected in the peritoneal washings from a treated case of serous cystadenocarcinoma with papillary involvement, stage III, was a clone of pseudodiploid cells. They were found after 12 months of chemotherapy. No supporting evidence of malignancy was found cytologically. Relatively simple karyotypes were obtained from metaphases found in the ascitic fluid of a patient surgically treated for an immature teratoma, stage II, grade 3. Consistent abnormalities found were trisomy 2, del(3)(p14), and der(5)t(5;8)(q33;q11). Of prime interest in a case of dysgerminoma, stage IV, was the finding of the isochromosome i(12p), a recognized nonrandom abnormality of malignant testicular tumors [1-5].

Primary cytogenetic abnormality detected in an endometrial adenocarcinoma.

Cytogenetic findings obtained from an endometrial adenocarcinoma stage 1A are reported. The primary stem line was pseudodiploid with an abnormal chromosome #8. Three side lines were noted, which collectively involved chromosomes X, #8, #12, and two members of group D. A small percentage of cells was either pseudotetraploid or near-tetraploid. Double minutes were noted in one of the latter cells. Interest in the case is centered on the finding of what appeared to be the primary chromosomal change.

Establishment of a human medulloblastoma cell line and its heterotransplantation into nude mice.

A permanent cell line arising from a cerebellar medulloblastoma was established and its growth characteristics were investigated. Although the original tumor inoculum failed to take, the cultured cells were readily tumorigenic in nude mice and gave rise to rapidly growing tumors which could be easily subpassaged. The primary tumor showed evidence of both glial and neuronal differentiation, and retention of neuronal differentiation, albeit minimal, occurred in both the cultured neoplastic cells and the nude mouse tumors. Glial differentiation, on the other hand, could not be demonstrated. G-banding analysis of the chromosomes present in the cell line showed that they were exclusively human.