Low adhesiveness coupled with high superinvasiveness in vitro predicts the in vivo metastatic potential of a mouse mammary adenocarcinoma cell line.
BACKGROUND
We have previously shown that the selection of cancer cell lines with chemotherapeutic agents can alter the invasive potential of the cells, resulting in a superinvasive phenotype, where cells not only invade through matrigel and migrate through membrane pores, but also subsequently detach from the underside of the invasion chamber, survive in suspension and ultimately attach to and grow on the bottom of the well beneath the insert. In order to determine the significance of this in vivo, the following experiments were performed.


METHODS
4T1-GFP mouse mammary adenocarcinoma cells were pulse-selected with doxorubicin or paclitaxel. Three variants with differing invasiveness were isolated and their metastatic potential in vivo was compared to the parental cell line, through injection into the mammary fat pad of BALB/c mice and subsequent primary tumour growth and metastasis to the lungs measurement.


RESULTS
Increasing superinvasiveness was inversely linked to tumour diameter (p < 0.005). The superinvasive status predicted the incidence of lung nodules in 2/3 variant groups, with significant differences in the number of nodules (p < 0.001).


CONCLUSIONS
The in vitro superinvasive phenotype coupled with decreased adhesion may predict for metastatic potential in vivo.
Glynn
Sharon A
SA
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Republic of Ireland.
Adams
Aine
A
Gibson
Brian
B
Cronin
Deirdre
D
Harmey
Judith H
JH
Clynes
Martin
M
D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004317:Doxorubicin / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology
D004317:Doxorubicin; D017239:Paclitaxel