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Transcriptomic signature of cell lines isolated from canine mammary adenocarcinoma metastases to lungs

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Krol M., Polanska J., Pawlowski K. M., Turowski P., Skierski J., Majewska A., Ugorski M., Morty R. E., Motyl T.

Journal of Applied Genetics

2010

vol. 51

issue 1

37-50

Metastasis is a final step in the progression of mammary gland cancer, usually leading to death. Potentially, a molecular signature of metastasis can be defined via comparison of primary tumors with their metastases. Currently, there is no data in the literature regarding the molecular portrait of metastases in dogs and only few reports regarding human cancer. This is the first report describing the transcriptomic signature of canine cancer metastatic cells. Two adenocarcinoma cell lines isolated from the canine mammary gland (CMT-W1 and CMT-W2) were compared with cell lines isolated from their lung metastases (CMT-W1M and CMT-W2M) with regards to the following cytometric parameters: cell cycle, ploidy, Bcl-2 expression, susceptibility to induced apoptosis, and transcriptomic profile. Cytometric analyses revealed significant differences in cell cycle and antiapoptotic potential between the examined cells. Using oligonucleotide microarrays, we found 104 up-regulated genes in the metastatic cell line CMT-W1M and 21 up-regulated genes in the primary CMT-W1 cell line. We also found 83 up-regulated genes in the CMT-W2M cell line and only 21 up-regulated genes in the CMT-W2 cell line. Among the up-regulated genes in both metastatic cell lines, we found 15 common genes. These differently expressed genes are involved mainly in signal transduction, cell structure and motility, nucleic acid metabolism, developmental processing, and apoptosis (GHSR, RASSF1, ARF1GAP, WDR74, SMOC2, SFRP4, DIAPH1, FSCN1, ALX4, SNX15, PLD2, WNT7B, POU6F2, NKG7, and POLR2F). Seven of them are involved in a cellular pathway dependent on ghrelin via growth hormone secretagogue receptor (GHSR). Our results suggest that this pathway may be essential for mammary cancer cells to have a metastatic potential.

Transcriptomic 'portraits' of canine mammary cancer cell lines with various phenotypes

100%

Krol M., Pawlowski K. M., Skierski J., Turowski P., Majewska A., Polanska J., Ugorski M., Morty R. E., Motyl T.

Journal of Applied Genetics

2010

vol. 51

issue 2

169-183

In light of the high incidence of mammary cancer in dogs and completion of the canine genome sequencing, the new possibilities of gene profiling by using DNA microarrays give hope to veterinary oncology. The cell lines isolated from mammary tumors are a valuable tool in developing and testing new pathway-specific cancer therapeutics. Differential cytometric analysis of 6 canine mammary cancer cell lines was performed. We divided cell lines into 3 groups based on their phenotype: 2 lines with high proliferative potential, 2 lines with high antiapoptotic potential, and 2 lines with high metastatic potential. DNA microarray analysis revealed common genes for cell lines of each group. We found that genes encoding the receptors for growth hormone and ghrelin are related to high proliferation rate, while ABR (active BCR-related) and TMD1 (TM2 domain containing 1) genes are related to a high antiapoptotic potential of the cancer cells. Metastatic properties of mammary cancer cells seem to be associated with elevated expression of PGP (P glycoprotein), SEMA3B (semaphorin 3B), and STIM1 (stromal interaction molecule 1).

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2 Journal of Applied Genetics

2 2010

2 Krol M.

2 Majewska A.

2 Morty R. E.

2 Motyl T.

2 Pawlowski K. M.

2 Polanska J.

2 Skierski J.

2 Turowski P.

2 Ugorski M.

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Transcriptomic signature of cell lines isolated from canine mammary adenocarcinoma metastases to lungs

Transcriptomic 'portraits' of canine mammary cancer cell lines with various phenotypes