Expression profiling of primary tumors and matched lymphatic and lung metastases in a xenogeneic breast cancer model.
Using a purpose-designed experimental model, we have defined new, statistically significant, differences in gene expression between heavily and weakly metastatic human breast cancer cell populations, in vivo and in vitro. The differences increased under selection pressures designed to increase metastatic proficiency. Conversely, the expression signatures of primary tumors generated by more aggressive variants, and their matched metastases in the lungs and lymph nodes, all tended to converge. However, the few persisting differences among these selectively enriched malignant growths in the breast, lungs, and lymph nodes were highly statistically significant, implying potential mechanistic involvement of the corresponding genes. The evidence that has emerged from the current work indicates that selective enhancement of metastatic proficiency by serial transplantation co-purifies a subliminal gene expression pattern within the tumor cell population. This signature most likely includes genes participating in metastasis pathogenesis, and we document manageable numbers of candidates for this role. The findings also suggest that metastasis to at least two different organs occurs through closely similar genetic mechanisms.
Montel
Valerie
V
Rebecca and John Moores Comprehensive Cancer Center and Department of Pathology, University of California, San Diego, 9500 Gilman Drive, M/C 0912 La Jolla, CA 92093-0912, USA.
Huang
To-Yu
TY
Mose
Evangeline
E
Pestonjamasp
Kersi
K
Tarin
David
D
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary*; D008207:Lymphatic Metastasis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014183:Transplantation, Heterologous