Lymph node resection induces the activation of tumor cells in the lungs

Abstract

Lymph node (LN) dissection is a crucial procedure for cancer staging, diagnosis and treatment, and for predicting patient survival. Activation of lung metastatic lesions after LN dissection has been described for head and neck cancer and breast cancer. Preclinical studies have reported that dissection of a tumor‐bearing LN is involved in the activation and rapid growth of latent tumor metastases in distant organs, but it is also important to understand how normal (non‐tumor‐bearing) LN resection influences secondary cancer formation. Here, we describe how the resection of tumor‐bearing and non‐tumor‐bearing LN affects distant metastases in MXH10/Mo‐lpr/lpr mice. Tumor cells were administered intravenously and/or intranodally into the right subiliac lymph node (SiLN) to create a mouse model of lung metastasis. Luciferase imaging revealed that tumor cells in the lung were activated after resection of the SiLN, irrespective of whether it contained tumor cells. No luciferase activity was detected in the lungs of mice that did not undergo LN resection (excluding the intravenous inoculation group). Our results indicate that resection of an LN can activate distant metastases regardless of whether the LN contains tumor cells. Hence, lung metastatic lesions are suppressed while metastatic LN are present but activated after LN resection. If this phenomenon occurs in patients with cancer, it is likely that lung metastatic lesions may be activated by elective LN dissection in clinical N0 cases. The development of minimally invasive cancer therapy without surgery would help to minimize the risk of activation of distant metastatic lesions by LN resection.

Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

“…32,59,60 In addition, our research group has shown that LN dissection induces activation of tumor cells that have metastasized to distant organs. 32,39,41,42 In summary, the rationale for LDDS targeting metastatic LN is to treat tumor tissue within metastatic LN, prevent distant metastasis of tumor cells from metastatic LN, avoid vascular damage, nerve damage, incisional infection, lymphedema 32,61 associated with LN removal, and the activation of tumor cells in distant organs associated with LN dissection and minimizing side effects. Therefore, the injection duration of chemotherapy drugs using the LDDS will be less than for the intratumoral or intralesion methods used in the clinic, and systemic toxicity will be less than for tumor-targeted therapy or In the future, optimizing factors, such as particle size, molecular weight, surface charge, lipophilicity, concentration, and the surface modification of biomaterials 32,46 to provide optimal osmolality and viscosity, will enable immunological strategies that can efficiently deliver biomaterials to these immune cells.…”

“…As previously stated, all in vivo experiments were carried out on mice under general anesthesia (2.5% isoflurane in oxygen), and great care was taken to reduce animal suffering. 32 , 39 , 40 , 41 , 42 The day on which the SiLN was inoculated with tumor cells was defined as day 0 I (Data S1 ).…”

Analysis of tumor vascularization in a mouse model of metastatic lung cancer

“…After depilation and skin disinfection, a minimally invasive approach was used for incision of the skin and exposure and extirpation of the tumor-bearing SiLN on day 3 post-inoculation for both cell types. Metastasis to the PALN and lung were assessed using the IVIS 18 at 6 h and on days 3, 6 and 9 post-inoculation of KM-Luc/GFP cells and days 7, 14, 21 and 28 post-inoculation of FM3A-Luc cells. Luciferin (15 mg/kg; Promega, Madison, WI, USA) was injected intraperitoneally into each mouse.…”

“…The excised organs from mice in the control group ( n = 4) were obtained on day 6 post-inoculation. Embedded specimens were serially sectioned (2 µm) and stained with EM or HE or immunostained for CD31 or Ki67 18 . Anti-CD31 staining to identify vascular endothelial cells was performed using an automated processor (Discovery, Ventana Medical Systems, Inc., Tucson, AZ, USA).…”

The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System

“…Cancer remains one of the leading causes of mortality worldwide, and most cases are due to lymph node (LN) metastasis [1]. To date, many measures have been developed to combat this trend, with remarkable therapeutic outcomes [2][3][4][5]; however, there is still a growing number of physical and emotional side effects associated with these protocols [6,7]. The destruction of tumour metastasis under hyperthermia has been investigated in the past few years as a non-invasive treatment method [8,9].…”