CEACAM1 and hollow spheroid formation modulate the chemosensitivity of colorectal cancer to 5-fluorouracil
CEACAM1 and hollow spheroid formation modulate the chemosensitivity of colorectal cancer to 5-fluorouracil
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DOI：
10.1007/s00280-014-2662-y
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发表时间：
2015-02-01
影响因子：
3
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
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作者：
Yamamoto, Naoyuki;Yokoyama, Shozo;Yamaue, Hiroki
癌胚抗原相关细胞粘附分子1 （CEACAM1）在结直肠癌侵袭前沿外重新表达并促进空心球体（HS）形成。本研究的目的是阐明CEACAM1细胞质结构域异构体平衡和HS是否与5-氟尿嘧啶（5FU）耐药性有关。采用二维(D)或三维培养系统评估CEACAM1细胞质异构体平衡和HS形成对结直肠癌细胞对5FU化疗敏感性的影响。根据82例行根治性手术加5fu化疗的III期结直肠癌患者HS的存在及各种临床病理特征，计算术后复发的危险因素。转染了CEACAM1-4L的HT29和表达了CEACAM1-4L和4S的亲代LS174T细胞对5FU的抗性明显高于转染了CEACAM1-4S或载体对照的细胞。在3D培养中，CEACAM1-4L诱导的HS形成诱导了对5FU的化学抗性，而CEACAM1-4S响应形成的固体球被5FU破坏。HS被确定为III期结直肠癌根治性切除后5fu化疗后复发的独立因素。Kaplan-Meier生存曲线显示HS患者的无复发生存率较低。CEACAM1长胞质结构域异构体优势和HS形成是与5FU耐药相关的表型。
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) re-expressed and promoted hollow spheroid (HS) formation beyond the invasion front of colorectal cancer. The aim of the present study was to clarify whether CEACAM1 cytoplasmic domain isoform balance and HS are associated with resistance to 5-fluorouracil (5FU).Two-dimensional (D) or 3D culture systems were employed to evaluate the effects of CEACAM1 cytoplasmic isoform balance and HS formation on the chemosensitivity of colorectal cancer cells to 5FU. The risk factors for postoperative recurrence were calculated based on the presence of HS and various clinicopathological characteristics in 82 patients with Stage III colorectal cancer who had undergone curative surgery followed by 5FU-based chemotherapy.CEACAM1-4L-transfected HT29 and CEACAM1-4L and 4S expressing parental LS174T cells had significantly higher resistance to 5FU in comparison with CEACAM1-4S- or vector control-transfected cells. In 3D culture, HS formation induced by CEACAM1-4L induced chemoresistance to 5FU, whereas the solid spheres formed in response to CEACAM1-4S were destroyed by 5FU treatment. HS was identified as an independent factor for recurrence of Stage III colorectal cancer after curative resection followed by 5FU-based chemotherapy. Kaplan-Meier survival curves demonstrated that patients with HS had lower recurrence-free survival rate.CEACAM1 long cytoplasmic domain isoform dominance and HS formation are phenotypes associated with chemoresistance to 5FU.