Seeding of epithelial cells into circulation during surgery for breast cancer: The fate of malignant and benign mobilized cells

被引：71

作者：

Camara O. ^{[1
]}

Kavallaris A. ^{[1
]}

Nöschel H. ^{[1
]}

Rengsberger M. ^{[2
]}

Jörke C. ^{[2
]}

Pachmann K. ^{[2
,3
]}

机构：

[1] Frauenklinik der Friedrich Schiller Universität Jena, D-07740 Jena

[2] Klinik für Innere Medizin II, Friedrich Schiller-Universität Jena, D-07747 Jena

[3] Transfusionsmedizinisches Zentrum Bayreuth, D-95448 Bayreuth

来源：

World Journal of Surgical Oncology | / 4卷 / 1期

关键词：

Breast Cancer; Epithelial Cell; Breast Cancer Patient; Circulate Tumor Cell; Increase Cell Number;

D O I：

10.1186/1477-7819-4-67

中图分类号：

学科分类号：

摘要：

Background: Surgery of malignant tumors has long been suspected to be the reason for enhancement of growth of metastases with fatal outcome. This often prevented surgeons from touching the tumor if not absolutely necessary. We have shown in lung cancer patients that surgery, itself, leads to mobilization of tumor cells into peripheral blood. Some of the mobilized cells finding an appropriate niche might grow to form early metastases. Monitoring of tumor cell release during and the fate of such cells after surgery for breast cancer may help to reveal how metastases develop after surgery. Method: We used the MAINTRAC® analysis, a new tool for online observation of circulating epithelial cells, to monitor the number of epithelial cells before, 30 min, 60 min, three and seven days after surgery and during subsequent variable follow up in breast cancer patients. Results: Circulating epithelial cells were already present before surgery in all patients. During the first 30-60 min after surgery values did not change immediately. They started increasing during the following 3 to 4 days up to thousand fold in 85% of treated patients in spite of complete resection of the tumor with tumor free margins in all patients. There was a subsequent re-decrease, with cell numbers remaining above pre-surgery values in 58% of cases until onset of chemotherapy. In a few cases, where no further therapy or only hormone treatment was given due to low risk stage, cell numbers were monitored for up to three years. They remained elevated with no or a slow decrease over time. This was in contrast to the observation in a patient where surgery was performed for benign condition. She was monitored before surgery with no cells detectable. Epithelial cells increased up to more than 50 000 after surgery but followed by a complete reduction to below the threshold of detection. Conclusion: Frequently before but regularly during surgery of breast cancer, epithelial cells are mobilized into circulation. Part of these cells, most probably normal or apoptotic cells, are cleared from the circulation as also shown to occur in benign conditions. After resection even if complete and of small tumors, cells can remain in the circulation over long times. Such cells may remain "dormant" but might settle and grow into metastases, if they find appropriate conditions, even after years. © 2006 Camera et al; licensee BioMed Central Ltd.

引用

共 23 条

[1]

Bonadonna G., Moliterni A., Zambetti M., Daidone M.G., Pilotti S., Gianni L., Valagussa P., 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: Cohort study, BMJ, 330, pp. 217-220, (2005)

[2]

Schmidt-Kittler O., Ragg T., Daskalakis A., Granzow M., Ahr A., Blankenstein T.J., Kaufmann M., Diebold J., Arnholdt H., Muller P., Bischoff J., Harich D., Schlimok G., Riethmuller G., Eils R., Klein C.A., From latent disseminated cells to overt metastasis: Genetic analysis of systemic breast cancer progression, PNAS, 100, pp. 7737-7742, (2003)

[3]

Pachmann K., Camara O., Kavallaris A., Schneider U., Schunemann S., Hoffken K., Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: A new tool for therapy monitoring, Breast Cancer Res, 7, (2005)

[4]

Meng S., Tripathy D., Frenkel E.P., Shete S., Naftalis E.Z., Huth J.F., Beitsch P.D., Leitch M., Hoover S., Euhus D., Haley B., Morrison L., Fleming T.P., Herlyn D., Terstappen L.W., Fehm T., Tucker T.F., Lane N., Wang J., Uhr J.W., Circulating tumor cells in patients with breast cancer dormancy, Clin Cancer Res, 10, pp. 8152-8162, (2004)

[5]

Pachmann K., Long-time recirculating tumor cells in breast cancer patients, Clin Cancer Res, 11, pp. 5657-5658, (2005)

[6]

Demicheli R., Miceli R., Moliterni A., Zambetti M., Hrushesky W.J., Retsky M.W., Valagussa P., Bonadonna G., Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process, Ann Oncol, 16, pp. 1449-1457, (2005)

[7]

Janni W., Rack B., Schindlbeck C., Strobl B., Rjosk D., Braun S., Sommer H., Pantel K., Gerber B., Friese K., The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence, Cancer, 103, pp. 884-891, (2005)

[8]

Braun S., Marth C., Circulating tumor cells in metastatic breast cancer-toward individualized treatment?, N Engl J Med, 351, pp. 824-826, (2004)

[9]

Pachmann K., Heiss P., Demel U., Tilz G., Detection and quantification of small numbers of circulating tumour cells in peripheral blood using laser scanning cytometer (LSC), Clin Chem Lab Med, 39, pp. 811-817, (2001)

[10]

Pachmann K., Clement J.H., Schneider C.P., Willen B., Camara O., Pachmann U., Hoffken K., Standardized quantification of circulating peripheral tumor cells from lung and breast cancer, Clin Chem Lab Med, 43, pp. 617-627, (2005)

← 1 2 3 →