Intranodal pressure of a metastatic lymph node reflects the response to lymphatic drug delivery system

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.

Keywords: breast cancer; cancer treatment; drug delivery; intranodal pressure; lymph node metastasis.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Female
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Mice
  • Neovascularization, Pathologic / diagnostic imaging
  • Neovascularization, Pathologic / pathology
  • Ultrasonography / methods
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents