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

Justin K. Smit; Hette Faber; Maarten Niemantsverdriet; Mirjam Baanstra; Johan Bussink; Harry Hollema; Ronald P. van Os; John Th. M. Plukker; Robert P. Coppes

doi:10.1016/j.radonc.2013.03.027

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

Justin K. Smit, Hette Faber, Maarten Niemantsverdriet, Mirjam Baanstra, Johan Bussink, Harry Hollema, Ronald P. van Os, John Th. M. Plukker, Robert P. Coppes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

47 Citations (Scopus)

Abstract

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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

Original language	English
Pages (from-to)	434-441
Number of pages	8
Journal	Radiotherapy and Oncology
Volume	107
Issue number	3
DOIs	https://doi.org/10.1016/j.radonc.2013.03.027
Publication status	Published - Jun-2013

Keywords

Esophageal cancer
Radiotherapy
Response
Chemoradiotherapy
Cancer stem cells
LOCAL TUMOR-CONTROL
NEOADJUVANT CHEMORADIOTHERAPY
INITIATING CELLS
CARCINOMA
SURVIVAL
ADENOCARCINOMA
IDENTIFICATION
RADIATION
LINES
RECURRENCE

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Cite this

@article{3af14d6aff2e44949397b49060eb5396,

title = "Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers",

abstract = "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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.",

keywords = "Esophageal cancer, Radiotherapy, Response, Chemoradiotherapy, Cancer stem cells, LOCAL TUMOR-CONTROL, NEOADJUVANT CHEMORADIOTHERAPY, INITIATING CELLS, CARCINOMA, SURVIVAL, ADENOCARCINOMA, IDENTIFICATION, RADIATION, LINES, RECURRENCE",

author = "Smit, {Justin K.} and Hette Faber and Maarten Niemantsverdriet and Mirjam Baanstra and Johan Bussink and Harry Hollema and {van Os}, {Ronald P.} and Plukker, {John Th. M.} and Coppes, {Robert P.}",

year = "2013",

month = jun,

doi = "10.1016/j.radonc.2013.03.027",

language = "English",

volume = "107",

pages = "434--441",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "ELSEVIER IRELAND LTD",

number = "3",

}

Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers. / Smit, Justin K.; Faber, Hette; Niemantsverdriet, Maarten; Baanstra, Mirjam; Bussink, Johan; Hollema, Harry; van Os, Ronald P.; Plukker, John Th. M.; Coppes, Robert P.

In: Radiotherapy and Oncology, Vol. 107, No. 3, 06.2013, p. 434-441.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Prediction of response to radiotherapy in the treatment of esophageal cancer using stem cell markers

AU - Smit, Justin K.

AU - Faber, Hette

AU - Niemantsverdriet, Maarten

AU - Baanstra, Mirjam

AU - Bussink, Johan

AU - Hollema, Harry

AU - van Os, Ronald P.

AU - Plukker, John Th. M.

AU - Coppes, Robert P.

PY - 2013/6

Y1 - 2013/6

N2 - 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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

AB - 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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

KW - Esophageal cancer

KW - Radiotherapy

KW - Response

KW - Chemoradiotherapy

KW - Cancer stem cells

KW - LOCAL TUMOR-CONTROL

KW - NEOADJUVANT CHEMORADIOTHERAPY

KW - INITIATING CELLS

KW - CARCINOMA

KW - SURVIVAL

KW - ADENOCARCINOMA

KW - IDENTIFICATION

KW - RADIATION

KW - LINES

KW - RECURRENCE

U2 - 10.1016/j.radonc.2013.03.027

DO - 10.1016/j.radonc.2013.03.027

M3 - Article

VL - 107

SP - 434

EP - 441

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

SN - 0167-8140

IS - 3

ER -