Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here, we report evidence of critical role for the angiopoietin-like protein 2 (ANGPTL2) in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In patients with lung cancer, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor cell-derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor cell-derived ANGPTL2 accelerated metastasis and shortened survival whereas attenuating ANGPTL2 expression in tumor cells-blunted metastasis and extended survival. Overall, our findings showed that tumor cell-derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process. Cancer Res; 72(7); 1784-94. Ó2012 AACR.

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We should utilize these prognostic factors to detect patients who might benefit from surgery. Therefore, we should periodically follow up advanced colorectal cancer patients by chest computed tomography to detect small pulmonary metastases before serum CEA elevation. Metastases to the lung or organs upstream from the lung are regarded as semi-local for colorectal cancer. This concept provides a rationale for validating surgical indications for pulmonary metastases from colorectal cancer.

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Pleurodesis is a minimally invasive technique that is effective in preventing postoperative recurrences of pneumothorax when added to VATS bullectomy. Additional pleurodesis has no disadvantages vs bullectomy alone in terms of worsening postoperative chest pain or pulmonary function.

The identification of sentinel nodes with (99m)Tc tin colloid is a reliable method of establishing the first site of nodal metastasis in non- small cell lung cancer. Sentinel nodes could be hardly identified in patients with a low ratio of forced expiratory volume in 1 second to forced vital capacity because of such conditions as chronic obstructive pulmonary disease. In vivo identification of sentinel nodes in the mediastinum could be useful approach to guide mediastinal lymph node sampling or dissection.

We identified that patients with a DFI less than 12 months who underwent pulmonary metastasectomy for metastases from esophageal cancer had a worse prognosis. Pulmonary metastasectomy for esophageal cancer should be considered for selected patients with a DFI >/=12 months.

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