Department of Oncology, Lund University, Lund, Sweden.
BMC Cancer. 2013 Jan 25;13:33. doi: 10.1186/1471-2407-13-33.
Local recurrence is a major factor affecting survival after treatment for head and neck squamous cell carcinoma (HNSCC). It is possible that the normal processes involved in wound healing after surgical removal of a primary tumor can boost the regrowth of residual cancer cells, thereby contributing to the recurrent growth. In this work, we collected human wound fluids and used them to investigate the effect of wound healing factors on HNSCC cell lines in vitro.
Wound fluids were collected from thyroidectomized patients diagnosed with benign disease and were included in assays of cell proliferation, migration, cell scattering, and invasion. The involvement of intracellular signaling pathways and membrane receptors were investigated by western blotting and the inclusion of specific inhibitors.
One out of four cell lines was greatly stimulated in proliferation, migration, cell scattering, and invasion by the addition of wound fluid as compared with addition of fetal bovine or human serum. These effects were accompanied by a sharp increase in activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response. Several of the observed phenotypic changes were epithelial-to-mesenchymal transition (EMT)-like, but the appropriate changes were not seen in any of the EMT markers investigated. The involvement of c-Met or epidermal growth factor receptor family members was excluded, while the interleukin-6 receptor was found to be partly responsible for the activation of STAT3.
In conclusion, we found cell-line-specific effects of wound healing factors on HNSCC, setting the stage for therapy development and predictive opportunities.
局部复发是影响头颈部鳞状细胞癌（HNSCC）治疗后生存的主要因素。手术切除原发性肿瘤后参与伤口愈合的正常过程可能会促进残留癌细胞的再生，从而导致肿瘤的复发性生长。在这项工作中，我们收集了人类伤口液，并将其用于体外研究伤口愈合因子对 HNSCC 细胞系的影响。
从诊断为良性疾病的甲状腺切除术患者中收集伤口液，并将其用于细胞增殖、迁移、细胞散射和侵袭的测定。通过 Western blot 分析和包含特定抑制剂来研究细胞内信号转导途径和膜受体的参与情况。
与添加胎牛血清或人血清相比，有一条 HNSCC 细胞系在添加伤口液后，在增殖、迁移、细胞散射和侵袭方面受到强烈刺激。这些作用伴随着信号转导和转录激活因子 3（STAT3）的强烈激活。STAT3 激活的抑制消除了伤口液的反应，表明 STAT3 在伤口愈合反应中起着重要作用。观察到的一些表型变化类似于上皮间质转化（EMT），但在所研究的 EMT 标志物中均未出现适当的变化。排除了 c-Met 或表皮生长因子受体家族成员的参与，而白细胞介素 6 受体被发现部分负责 STAT3 的激活。
总之，我们发现伤口愈合因子对 HNSCC 具有细胞系特异性影响，为治疗开发和预测机会奠定了基础。
