title: Impact of host ageing on the metastatic phenotype.
abstract: Ageing impacts multiple host mechanisms involved in cancer progression. Here we show that poorly metastatic Lewis lung carcinoma (LLC) cells form less bulky metastatic deposits in aged mice (>52 weeks) relative to their young (4-6 weeks) counterparts. Serial selection of LLC cells for increased metastatic capability in either young or old mice led in both cases to exaggerated growth of pulmonary nodules after only 5 cycles of in vivo passage. The respective metastatic cellular variants established in young (Y-series) or old (O-series) mice differed in cell morphology and constitutive activity of growth factor receptors, especially phospho-PDGFRa and phospho-EPHA7. These cell lines also exhibited marked differences in their time dependent profiles of cellular impedance (CI), which reflects their physical properties, such as cell shape, adhesion and interactions with substrata. In confluent monolayer culture Y-series cell lines generated high and increasing CI values, while these values remained low and constant in the O-series of cell lines. These observations suggest that the selective pressure of the metastatic microenvironment in young versus old hosts is sufficiently different to results in the enrichment of distinct, age-related metastatic phenotypes of cancer cells. Thus, age could inform therapeutic approaches to metastatic cancers.
authors: Montreal Children's Hospital, RI MUHC, McGill University, Montreal, Quebec, Canada.
authors: Brian
authors: B
authors: Meehan
authors: Alexander
authors: A
authors: Dombrovsky
authors: Karrie
authors: K
authors: Lau
authors: Tiffany
authors: T
authors: Lai
authors: Nathalie
authors: N
authors: Magnus
authors: Laura
authors: L
authors: Montermini
authors: Janusz
authors: J
authors: Rak
mesh_terms: D000375:Aging; D000818:Animals; D018827:Carcinoma, Lewis Lung; D002448:Cell Adhesion; D002453:Cell Cycle; D048430:Cell Shape; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation; D013997:Time Factors