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Are Apoptotic Bodies Involved? An Experimental Study in a Rat Cancer Model
a Experimental Research Unit, General University Hospital of Albacete, Albacete, Spain b Department of Haematology, General University Hospital of Albacete, Albacete, Spain c Department of Surgery, Universidad Autónoma de Madrid and La Paz University Hospital, Madrid, Spain
Key Words: apoptotic bodies • colon cancer • circulating nucleic acids • genometastasis
Address for correspondence: Prof. Damián García-Olmo, Servicio de Cirugía General—C, Hospital Universitario "La Paz," Paseo Castellana 261, 28046 Madrid, Spain. Voice: +34-917-27-70-00; fax: +34-967-24-39-52. e-mail: damian.garcia{at}uam.es
The "genometastasis hypothesis" proposes that cell-free tumor nucleic acids might be able to transform host stem cells, and that this might be a pathway for the development of metastases. This theory is supported by previous experimental findings and is consistent with observations of other authors. It has been suggested that tumor DNA might be horizontally transferred by the uptake of apoptotic bodies and initiate the genetic changes that are necessary for tumor formation. In addition, apoptotic bodies have been proposed as possible vehicles that protect the nucleic acids circulating in the plasma from enzymatic degradation. In the present study, we analyzed the presence of apoptotic bodies in serum and its relationship with tumor progression in a heterotopic model of colon cancer in the rat. We injected DHD/K12-PROb cancer cells subcutaneously into BD-IX rats and divided the animals into three groups according to the time between the injection of tumor cells and euthanasia. A control group of healthy animals was included (n = 6). After euthanasia, macroscopic metastases were assessed and samples of blood were collected. To detect apoptotic bodies in the sera, each sample was mixed with FITC-conjugated annexin V antibody in combination with propidium iodide and then analyzed by flow cytometry. Detection of apoptotic bodies was only significantly increased in the sera of a few tumor-bearing animals in late stages of tumor development. Thus, such particles appear not to be the vehicle of the cell-free tumor nucleic acids that are detected at early stages of cancer.
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