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Identification and characterization of stem-like cancer cells in prostate tumor recurrence after radiotherapy.

机译：放射治疗后前列腺肿瘤复发中干细胞样癌细胞的鉴定和表征。

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摘要

Radiotherapy is a primary treatment modality for prostate cancer but its efficacy is limited by the recurrence of resistant tumors. Cancer stem cells (CSCs), also known as tumor initiating cells, are a small subset of tumor cells that are responsible for transplantability of tumors, but its role in tumor recurrence after treatment remains unproven. To investigate the biology of CSCs in tumor recurrence after radiotherapy, tumor cells were irradiated in vitro and then injected s.c. into mice to model tumor recurrence from radioresistant tumor cells. It was found that DU145 cells, after irradiation at 800 cGy, were still able to form palpable tumors but the growth of tumors was significantly compromised. To investigate whether CSCs survived from radiation and gave rise to radioresistant tumors, we evaluated the presence of CD133 antigen, a putative marker for stem cells, in the recurring tumors by immunohistochemistry. Most cells were negative for CD133 antigen in tumors derived from sham-irradiated cells. In the small recurrent tumors derived from irradiated cells, most cells were positive for CD133 antigens, but when the tumors grew bigger, the CD133 positivity was reduced. To further study the role of CSCs in radioresistance, we enriched and expanded CSCs from DU145 or LNCaP cells as prostaspheres. The cells in prostaspheres retained a high percentage of CD133(+) cells and were able to differentiate in serum-rich media and form tumors when transplanted into mice. When compared to isogenic parental DU145 cells, the CSCs isolated from DU145 presented a higher resistance toward radiation at 200 and 800 cGy as indicated by colony formation assay. CSCs isolated from LNCaP cells presented a much higher resistance toward radiation at 800 and 2,000 cGy than parental LNCaP cells. Taken together, our data suggest that prostate CSCs are inherently more resistant to radiotherapy than non-CSCs and surviving CSCs may lead to recurrence of tumors after radiotherapy.
机译：放射疗法是前列腺癌的主要治疗方式，但其疗效受到耐药性肿瘤复发的限制。癌症干细胞（CSC），也称为肿瘤起始细胞，是负责肿瘤移植性的一小部分肿瘤细胞，但在治疗后其在肿瘤复发中的作用尚未得到证实。为了研究放射治疗后CSCs在肿瘤复发中的生物学性，将肿瘤细胞进行体外照射，然后进行皮下注射。进入小鼠以模拟抗辐射肿瘤细胞的肿瘤复发。发现在以800cGy照射后，DU145细胞仍然能够形成明显的肿瘤，但是肿瘤的生长受到显着损害。为了研究CSCs是否能从放射线中幸存下来并引起放射线敏感性肿瘤，我们通过免疫组织化学方法评估了复发性肿瘤中CD133抗原（干细胞的公认标志物）的存在。在源自假照射细胞的肿瘤中，大多数细胞的CD133抗原均为阴性。在源自辐射细胞的小型复发性肿瘤中，大多数细胞对CD133抗原呈阳性，但当肿瘤变大时，CD133阳性率降低。为了进一步研究CSC在放射抗性中的作用，我们丰富和扩展了DU145或LNCaP细胞中的CSC作为前列腺素。前球体内的细胞保留了高百分比的CD133（+）细胞，能够在富含血清的培养基中分化并在移植到小鼠中时形成肿瘤。与同基因的亲本DU145细胞相比，从DU145分离的CSC表现出对200和800 cGy辐射的更高抵抗力，如菌落形成试验所表明的。与亲本LNCaP细胞相比，从LNCaP细胞分离的CSC在800 cGy和2,000 cGy时表现出更高的抗辐射能力。两者合计，我们的数据表明，前列腺CSCs本质上比非CSCs更耐放射治疗，幸存的CSCs可能导致放疗后肿瘤复发。

著录项

  • 作者

    Wang, Man-Tzu.;

  • 作者单位

    Southern Illinois University at Carbondale.;

  • 授予单位 Southern Illinois University at Carbondale.;
  • 学科 Biology Cell.;Health Sciences Oncology.
  • 学位 M.S.
  • 年度 2008
  • 页码 61 p.
  • 总页数 61
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;肿瘤学;
  • 关键词

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