Cytogenetic changes during tumor progression towards invasion, metastasis and immune escape in the Eb/ESb model system

Abstract

Related tumor lines which represent different stages in their progression towards metastatic capacity were investigated and compared at the chromosomal level. The parental low-metastatic tumor line (L5178Y/Eb) was derived from a long-term transplanted, chemically induced T-cell lymphoma of the DBA/2 mouse. The cytogenetic analysis included this Eb line, a spontaneous high metastatic variant thereof which expressed a distinct tumor-associated transplantation antigen (ESb TATA+), and an immunoresistant TATA-negative variant of the latter (ESb TATA-). All three cell lines were characterized by a near-diploid chromosome count and by some common chromosomal markers derived from Nos. 6, 13 and 16 Large-scale chromosomal rearrangments resulted in the formation of eight marker chromosomes in Eb cells, 16 in ESb TATA+ cells and 18 in ESb TATA- cells. Tumor progression in this system showed a tendency to monosomies, which could bring the corresponding genes to a hemizygous state and possibly to a release from repression. Chromosome 15 was trisomic in Eb cells, monosomic in ESb TATA+ cells and hardly detectable in ESb TATA- cells. The Ig heavy-chain gene-carrying region of both chromosomes No. 12 was found in translocation with chromosomes Nos. 5, 13 and 14 (Eb cells) and with Nos. 1 and 17 (ESb cells). ESb TATA- cells differed from ESb TATA+ cells at four different chromosomes (Nos. 5, 8, 14 and 15).

Comparative Analysis of Oncogene Expression and Chromosome Abnormalities between Metastatic and Nonmetastatic B16 Melanoma Clones

“…Dzarlieva et al [35] performed cyto genetic analysis of chemically induced T cell lymphoma of the DBA/2 mouse in its lowmetastatic cell line and high-metastatic vari ants. They reported that tumor progression in their system was accompanied by a ten dency to monosomies of chromosomes 4, 14, 15, 18, and 19.…”

Tumor Progression to Malignancy: A Discussion of the Unifying Role of the Cytoskeleton

“…In many malignancies, cytogenetic studies reveal a wide variety of chromosomal aberrations (duplications, deletions, and translocations) [1][2][3] and aneuploidy, especially hyperploidy 4,5 . Large hyperchromatic nuclei are a common diagnostic feature of malignant cells.…”

“…Karyotypic aberrations such as translocations, inversions, insertions, partial deletions, and ring formation are observable in many types of malignant cells. [1][2][3] Amplification or deletion of genes that normally regulate tubulin synthesis and microtubule polymerization and depolymerization, for example through protein phosphorylation regulatory pathways, are likely to lead to further errors in chromatid segregation during mitosis. Each successive asymmetric mitosis results in further deviation from the normal karyotype and genetic content.…”

“…37,38 The incidence of partial or full monosomies and translocations has been correlated with increasing metastatic potential in mouse lymphoma cell lines. 3 Therefore, tumor stem cells are not necessarily metastatic initially, but a small fraction may develop metastatic properties in the course of anaplastic progression and increasingly deficient microtubule regulation. Under selection pressure resulting from the use of a cytotoxic drug, this same genetic variability provides the basis for the emergence of drug-resistant cell lines.…”

“…Cytogenetic studies of DNA content and chromosome number may also have prognostic value since they may reflect histologic subtypes. 2,3,5 This view of malignant progression suggests that intensive first-course combination chemotherapy and mixed modalities are preferable over single drugs and single modalities in advanced cases. 39,40 Use of different drugs simultaneously improves targeting of heterogenous tumor cell populations.…”