In vivo overexpression of c-erbB-2 oncoprotein in xenografts of mice implanted with human colon cancer lines

We have previously shown that c-erbB-2 oncoprotein encoded by the erbB-2 gene is overexpressed in human colorectal cancers that metastasise compared to those that are cured by surgery. To determine whether c-erbB-2 is also differentially expressed in vivo in metastasising and non-metastasising tumours, we developed models of colorectal cancer growth in nude mice. Human colon cancer cell lines, HCT116, KM12SM, LIM1215 and SW480, were injected into the caecum after characterising their morphology, doubling time, DNA flow-cytometry and expression of c-erbB-2. Six weeks later, xenografted tissues were fixed for histological analysis and detection of c-erbB-2 by immunohistochemistry. 78% (21/27) of mice developed caecal cancers. The caecal tumours derived from HCT116, KM12SM or LIM1215 were highly metastatic: 67 to 100% of them had liver metastases and lymph node involvement and 33 to 75% had lung tumours. Most of the tumours were c-erbB-2-positive. In contrast SW480 caecal tumours had only 33% lymph node involvement, but not liver or lung metastases. Only one SW480 caecal tumour and one lymph node metastasis expressed c-erbB-2. C-erbB-2 was more frequently expressed in xenografted tissues in colon cancer primaries and secondaries of the highly metastatic cells (HCT116, KM12SM and LIM1215) crompared to the cells (SW480) giving predominantly local growth. Our results suggest that c-erbB-2 gene may play an important role in the development of metastasis from colorectal cancer.