Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon.
Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
Langdon
S P
SP
ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
Rabiasz
G J
GJ
Anderson
L
L
Ritchie
A A
AA
Fergusson
R J
RJ
Hay
F G
FG
Miller
E P
EP
Mullen
P
P
Plumb
J
J
Miller
W R
WR
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000473:pathology* / Q000628:therapy / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000628:therapy / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D008875:Middle Aged; D014183:Transplantation, Heterologous
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D007372:Interferons; D003402:Creatine Kinase; D004296:Dopa Decarboxylase