Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, 4-1, Sendai, Aoba, Miyagi, 9808575, Japan.
Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
Cancer Sci. 2020 Nov;111(11):4232-4241. doi: 10.1111/cas.14640. Epub 2020 Sep 18.
Cancer metastasis to lymph nodes (LNs) almost certainly contributes to distant metastasis. Elevation of LN internal pressure (intranodal pressure, INP) during tumor proliferation is associated with a poor prognosis for patients. We have previously reported that a lymphatic drug delivery system (LDDS) allows the direct delivery of anticancer drugs into the lymphatic system and is a promising treatment strategy for early-stage LN metastasis. However, methods for evaluating the treatment effects have not been established. Here, we used a mouse model of MXH10/Mo-lpr/lpr, which develops a systemic swelling of LNs, and murine malignant fibrous histiocytoma-like (KM-Luc/GFP) cells or murine breast cancer (FM3A-Luc) cells inoculated into the subiliac LN of mice to produce a tumor-bearing LN model. The changes in INP during intranodal tumor progression and after treatment with cis-dichlorodiammineplatinum(II) (CDDP) using an LDDS were measured. We found that tumor progression was associated with an increase in INP that occurred independently of LN volume changes. The elevation in INP was suppressed by CDDP treatment with the LDDS when intranodal tumor progression was significantly inhibited. These findings indicate that INP is a useful parameter for monitoring the therapeutic effect in patients with LN metastasis who have been given drugs using an LDDS, which will serve to manage cancer metastasis treatment and contribute to an improved quality of life for cancer patients.
癌症转移至淋巴结(LNs)几乎肯定会导致远处转移。肿瘤增殖过程中 LNs 内部压力(INP)升高与患者预后不良相关。我们之前曾报道,淋巴药物递送系统(LDDS)可允许将抗癌药物直接递送至淋巴系统,是治疗早期 LN 转移的有前途的治疗策略。然而,尚未建立评估治疗效果的方法。在这里,我们使用了 MXH10/Mo-lpr/lpr 小鼠模型,该模型会导致 LNs 全身性肿胀,并用 KM-Luc/GFP 细胞或 FM3A-Luc 细胞接种到小鼠的髂下淋巴结中,产生了带瘤 LN 模型。通过 LDDS 测量了 INP 在 LNs 内肿瘤进展过程中和顺铂(CDDP)治疗后的变化。我们发现,肿瘤进展与 INP 的升高有关,而 INP 的升高与 LNs 体积变化无关。当 INP 内肿瘤进展受到明显抑制时,LDDS 中的 CDDP 治疗可抑制 INP 的升高。这些发现表明,INP 是监测接受 LDDS 给药治疗的 LN 转移患者治疗效果的有用参数,这将有助于管理癌症转移治疗,并提高癌症患者的生活质量。