Lung Cancer |

Development of an Orthotopic Human Non-small Cell Lung Cancer Model in Nude Mice by an Ultra-Minimally Invasive Transbronchial Approach FREE TO VIEW

Takahiro Nakajima*, MD; Takashi Anayama, MD; Yasushi Matsuda, MD; David Hwang, MD; Patrick McVeigh, PhD; Brian Wilson, PhD; Gang Zheng, PhD; Shaf Keshavjee, MD; Kazuhiro Yasufuku, MD
Author and Funding Information

Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada

Chest. 2012;142(4_MeetingAbstracts):594A. doi:10.1378/chest.1385549
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PRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PM

PURPOSE: Currently available orthotopic human non-small cell lung cancer (NSCLC) xenograft models utilize percutaneous delivery of tumor cells, which may result in pneumothorax, pleural dissemination and multifocal lesions. A clinically relevant preclinical model bearing a solitary nodule would be of value for a variety of research studies. The aim of the present work is to establish an ultra-minimally invasive orthotopic human NSCLC xenograft model in immunodeficient mice.

METHODS: Male athymic nude mice (NCr-Foxn1nu) and human NSCLC cell lines, including A549 (adenocarcinoma), H460 (large cell carcinoma) and H520 (squamous cell carcinoma), were used. Mice were anesthetized and placed in the supine recumbent position. Pulling the tongue laterally using a Mosquito-pean forcep allowed us to lift the lower jaw and expose the glottis. Under direct visualization of the vocal cords using a surgical microscope, a 23G blunt-tip slightly curved metal catheter was introduced into the trachea. A total of 50-70 µl of the tumor cell suspension (2.5x105 tumor cells) was mixed with MatrigelTM and administered into the lung. Mice were monitored using weekly microCT scans for tumor formation. When the tumor size reached more than 4 mm in diameter, the animals were sacrificed and the tumor tissue was evaluated histopathologically.

RESULTS: Of 26 mice (A549, n=17, H460, n=6, H520, n=3) studied, 23 were confirmed to have tumor formation. 19 developed solitary tumors and 4 mice had multifocal lesions. There was no evidence of extra-pleural dissemination or effusion. On examination of hematoxylin-eosin, elastic trichrome and CD31 stained sections, tumor cells were observed growing primarily within the alveolar structures. H460 tumors exhibited invasion into the bronchioles and visceral pleura. Differential EGFR expressions were also observed between each cell type by immunohistochemistry.

CONCLUSIONS: Transbronchial delivery of tumor cells enabled the establishment of a novel minimally invasive orthotopic human lung cancer xenograft model in mice.

CLINICAL IMPLICATIONS: This model will provide a clinically relevant in-vivo platform suitable for studies of imaging, tumor biology and novel therapeutic interventions in lung cancer.

DISCLOSURE: The following authors have nothing to disclose: Takahiro Nakajima, Takashi Anayama, Yasushi Matsuda, David Hwang, Patrick McVeigh, Brian Wilson, Gang Zheng, Shaf Keshavjee, Kazuhiro Yasufuku

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Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada




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