ABSTRACT
PURPOSE: Meticulous treatment strategies taking tumor heterogeneity into account are considered essential to achieve breakthroughs in current cancer therapy. We analyzed tumor heterogeneity in the primary tumor of a patient with pulmonary adenocarcinoma characterized by a poor prognosis. METHODS: Four sublines with different growth characteristics in vitro were established from the tumor using a method for short-term selective cultivation. We examined the differences in morphological, biochemical, and genetic findings of these sublines. RESULTS: Differences in the histological features of the transplanted tumors were seen in the four sublines. The 88-2T and 88-2 tumors revealed a well-differentiated adenocarcinoma; the 88-2F tumor revealed a large cell-like carcinoma resembling the metastatic tumor in the lymph nodes; and the 88-2FA tumor was composed of signet-ring cells. There were differences in oncogenes, with the 88-2F line alone exhibiting 12-fold amplification of c-myc. Sensitivity to cytosine arabinoside (Ara C) was specifically increased in the 88-2F cell line, alone. CONCLUSIONS: These sublines demonstrate that human pulmonary adenocarcinoma has various types of heterogeneity within the primary tumor. Furthermore, c-myc amplification may play an important role in altering phenotype and growth characteristics in vitro and in vivo, and for increasing sensitivity to Ara C and the potential of cancer cells to metastasize to lymph nodes.
