Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers

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• 作者：Justin K. Smit ; Hette Faber ; Maarten Niemantsverdriet ; Mirjam Baanstra ; Johan Bussink ; Harry Hollema ; Ronald P. van Os ; John Th. M. Plukker ; Robert P. Coppes
• 关键词：Esophageal cancer ; Radiotherapy ; Response ; Chemoradiotherapy ; Cancer stem cells
• 刊名：Radiotherapy and Oncology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：107
• 期：3
• 页码：434-441
• 全文大小：3738 K

文摘

Background and purpose

In this study, we investigated whether cancer stem cell marker expressing cells can be identified that predict for the response of esophageal cancer (EC) to CRT.

Materials and methods

EC cell-lines OE-33 and OE-21 were used to assess in vitro, stem cell activity, proliferative capacity and radiation response. Xenograft tumors were generated using NOD/SCID mice to assess in vivo proliferative capacity and tumor hypoxia. Archival and fresh EC biopsy tissue was used to confirm our in vitro and in vivo results.

Results

We showed that the CD44+/CD24? subpopulation of EC cells exerts a higher proliferation rate and sphere forming potential and is more radioresistant in vitro, when compared to unselected or CD44+/CD24+ cells. Moreover, CD44+/CD24? cells formed xenograft tumors faster and were often located in hypoxic tumor areas.

In a study of archival pre-neoadjuvant CRT biopsy material from EC adenocarcinoma patients (N = 27), this population could only be identified in 50 % (9/18) of reduced-responders to neoadjuvant CRT, but never (0/9) in the complete responders (P = 0.009).

Conclusion

These results warrant further investigation into the possible clinical benefit of CD44+/CD24? as a predictive marker in EC patients for the response to chemoradiation.