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Comparison of Intrapulmonary, Percutaneous Intrathoracic, and Subcutaneous Models for the Propagation of Human Pulmonary and Nonpulmonary Cancer Cell Lines in Athymic Nude Mice

Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute [T. L. M., R. H. S., B. J. A., J. G. M., M. R. B.] and Program Resources, Inc., [D. L. F.], Frederick Cancer Research Facility, Frederick, Maryland; and Departments of Surgical Pathology [J. C. E.], Radiology [M. E. B.], and Medicine [M. C. L.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The propagation efficiencies, growth patterns, histological appearances, and roeatgenographic demonstration of tumors derived from six continmous human pulmonary tumor cell lines implanted intrathoracically (i.t.) and intrabronchially (i.b.) were compared with the conventional s.c. implantation method at three different tumor cell inocula (N = 184, i.b.; N = 185, i.t.; N = 180, s.c.). A tumor-related mortality of 100% was noted when the six different human lung tumor cell lines, including A549 adenocarcinoma, NCI-H125 adenosquamous carcinoma, NCI-H460 large cell undifferentiated carcinoma, NCI-H69 small cell carcinoma, and NCI-H358 and NCI-H322 bronchioloalveolar cell carcinomas, were implanted i.b. at a 1.0 x 10⁶ tumor cell inoculum. A similar (92%) tumor-related mortality was observed when these same lung tumor cell lines were implanted i.t. at a 1.0 x 10⁶ tumor cell inoculum (P > 0.10), whereas minimal (5%) tumor-related mortality was noted when cells from the six different cell lines were implanted s.c. (P < 0.001). In addition, a dose-dependent, tumor-related mortality was noted for either i.t. or i.b. implantation when lower (1.0 x 10⁵ or 1.0 x 10⁴) tumor cell inocula were employed. Histological characteristics and growth patterns of tumors propagated employing the three implantation techniques were closely comparable for all three propagation methods and, in all instances, histological appearances of the tumors were representative of the current tumor cell lines from which they were derived. Approximately 30% of the lung tumors propagated i.t. grew in the chest wall and/or in the lung pareachyma as well as in the pleural space. In contrast, tumors propagated i.b. grew predominantly in the lung parenchyma. When five non-pulmonary human tumor cell lines (including U251 glioblastoma, LOX amelamontic melanoma, HT-29 colon adenocarcinoma, OVCAR 3 ovarian adenocarcinoma, and adriamycin-resistant MCF-7 breast adenocarcinoma) were propagated i.b. or i.t., there was considerable site-specific variability in tumor-related mortality depending on the tumor type. These data demonstrate that both the i.b. and i.t. models should be useful for the in vivo propagation and study of certain human pulmonary and nonpulmonary carcinomas as well as being advantageous for future studies of cancer biology and developmental therapeutics.

¹ To whom requests for reprints should be addressed, at Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research Facility, Building 428, Room 63, Frederick, MD 21701-1013.

Received 10/26/87. Revised 2/10/88. Accepted 2/17/88.

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