Amplification of the Y chromosome in three murine tumor cell lines transformed in vivo by different human prostate cancers

Abstract

Conventional and molecular cytogenetic analyses of three murine cancer cell lines that had been induced in male athymic mice by the injection of three different human prostate cancer cell lines revealed selective amplification of the Y chromosome. In particular, analysis of metaphase and interphase nuclei by fluorescence in situ hybridization (FISH) with the mouse Y chromosome-specific DNA painting probe revealed the presence of various numbers of Y chromosomes, ranging from one to eight, with a large majority of nuclei showing two copies (46.5-60.1%). In Interphase nuclei, the Y chromosomes showed distinct morphology, allowing identification irrespective of whether the preparations were treated for 15 min or for 5 h with Colcemid, a chemical known to cause chromosome condensation. However, FISH performed on human lymphocyte cultures with chromosome-specific DNA painting probes other than the Y chromosome did not reveal condensed chromosome morphology in interphase nuclei even after 12 h of Colcemid treatment. Our FISH results indicate that (1) the Y chromosome is selectively amplified in all three cell lines; (2) the mouse Y chromosome number is comparable in both interphase and metaphase cells: (3) the Y chromosome number varies between one and eight, with a large majority of cells showing two or three copies in most interphase nuclei; (4) the condensation of the Y chromosome is not affected by the duration of Colcemid treatment but by its inherent DNA constitution; and (5) the number of copies of the Y chromosome is increased and retained not only in human prostate tumor cell lines but also in murine tumors induced by these prostate tumor cell lines.

Challenges and Prospects of Patient-Derived Xenografts for Cancer Research

“…Anderson Cancer Center found a contamination rate of host cells as high as 39% in cell lines sent for authentication [31]. Several studies demonstrated murine stromal and mixed human/murine cells in prostate cancer, indicating that human cancer cells cross-talked to murine stromal cells [32][33][34]. These observations indicated that human prostate tumors were transformed by human tumor cells into mouse oncogenic cells.…”

“…Cancers 2023, 15, x FOR PEER REVIEW 10 of 19 cells [32][33][34]. These observations indicated that human prostate tumors were transformed by human tumor cells into mouse oncogenic cells.…”

“…Human-host oncogenic transformation in the PDXs is summarized in Figure 4A,B. The mechanism of how human cancer cells transformed murine stromal cells in PDXs is not yet fully understood [32][33][34]. There are two hypotheses: [1] cell fusion and horizontal signal transfer or transmission and [2] the transfer of cell-free DNA (cfDNA).…”

“…is not yet fully understood [32][33][34]. There are two hypotheses: [1] cell fusion and horizontal signal transfer or transmission and [2] the transfer of cell-free DNA (cfDNA).…”

A new intronic quantitative PCR method led to the discovery of transformation from human ascites to murine malignancy in a mouse model

“…A human-derived prostate tumor cell line in athymic nude mice produced human, murine stromal and mixed human/murine cells, suggesting that cancer cells are capable of transforming host stromal cells ( 5 ). Later on, three murine cancer cell lines had been induced by the injection of three different human prostate cancer cell lines, which revealed selective amplification of the Y chromosome ( 6 ). They had unique marker chromosomes involving mouse chromosome 12, with a common break point.…”