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Establishment and Characterization of a Human Lung Cancer Cell Line NCI-H460-LNM35 with Consistent Lymphogenous Metastasis via Both Subcutaneous and Orthotopic Propagation¹

Pathophysiology Unit [K .K., Y. T., Ta. T.], Laboratory of Immunology [Te. T., To. T.], and Laboratory of Ultrastructure Research [Ta. T.], Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Aichi 464-8681, Japan; Departments of Internal Medicine, Aichi Cancer Center Hospital [T. H.], Nagoya, Aichi 464-8681, Japan; and Laboratory of Pathology, Department of Basic Gerontology, National Institute for Longevity Sciences [O. M.], Ohbu, Aichi 474-8522, Japan

Lymphogenous metastasis is a common feature of human lung cancers, but very little is known about the underlying mechanism. In the present study, in vivo selection was carried out to obtain a highly lymphogenous metastatic subline of a human large cell carcinoma of the lung, NCI-H460. The resulting subline, termed NCI-H460-LNM35 (LNM35), was shown to metastasize to regional lymph nodes with a 100% incidence not only as a result of orthotopic intrabronchial (i.b.) implantation, but also as a result of conventional s.c. implantation. LNM35 has a short latency period, allowing for the collection of experimental data within 28 days after i.b. inoculation and 45 days after s.c. inoculation. It was noted that orthotopically i.b.-propagated LNM35 closely mimicked the clinical manifestations of human lung cancer patients by infiltrating into lymphatic vessels and metastasizing to the mediastinal lymph nodes. The LNM35 cell line is, to the best of our knowledge, the first human lung cancer cell line to be reported as having lymphogenous metastatic properties, and the observed 100% incidence by s.c. inoculation gives LNM35 a significant advantage even over previously reported human cancer cell lines of other origins. Comparisons between LNM35 and its parental NCI-H460 cell lines were also made with regard to expression levels and/or activities of various molecules that are thought to play a part in the metastatic process. We show here that the expression of cyclooxygenase 2 is increased in LNM35 and that a specific cyclooxygenase 2 inhibitor, nimesulide, can inhibit the invasion of LNM35 in vitro through Matrigel containing basement membrane components.

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