DISSEMINATION IN ATHYMIC NUDE-MICE OF LACZ TRANSFECTED SMALL-CELL LUNG-CANCER CELLS IDENTIFIED BY X-GAL STAINING

The small cell lung cancer cell lines GLC-2 and DMS 456 were genetical ly labeled with the lacZ gene and examined for invasive and metastatic potential in META/Bom(TM) nude mice. The lacZ gene encodes the enzyme beta-D-galactosidase, and cells expressing this enzyme were identifie d by staining with the chromogenic substrate X-gal. lacZ expressing ce lls were investigated after subcutaneous (s.c.) inoculation and intrav enous (i.v.) injection. The X-gal detection of beta-D-galactosidase ac tivity proved to be a rapid and easy means for specific and highly sen sitive identification of metastases. All primary s.c. tumors stained b y X-gal. The primary tumors of GLC-2 regularly demonstrated local inva sive growth and produced multiple metastases in several organs. In con trast, primary DMS 456 tumors only occasionally demonstrated local inv asion and very rarely generated secondary foci. No experimental metast ases were found after i.v. injection of the examined tumor lines. The results indicate an intratumoral heterogeneity among individual SCLC t umors in the capacity for invasion and metastatic spread. The differen t metastatic pattern of GLC-2 after s.c. and i.v. inoculation supports the hypothesis that initial steps of the metastatic cascade occurring in the primary tumor are necessary for the subsequent production of g rowing metastases.