Regional lymph node status is an important prognostic indicator of tumor aggressiveness. However, early diagnosis of metastasis using intranodal pressure, at a stage when lymph node size has not changed significantly, has not been investigated. Here, we use an MXH10/Mo‐lpr/lpr mouse model of lymph node metastasis to show that intranodal pressure increases in both the subiliac lymph node and proper axillary lymph node, which are connected by lymphatic vessels, when tumor cells are injected into the subiliac lymph node to induce metastasis to the proper axillary lymph node. We found that intranodal pressure in the subiliac lymph node increased at the stage when metastasis was detected by in vivo bioluminescence, but when proper axillary lymph node volume (measured by high‐frequency ultrasound imaging) had not increased significantly. Intravenously injected liposomes, encapsulating indocyanine green, were detected in solid tumors by in vivo bioluminescence, but not in the proper axillary lymph node. Basic blood vessel and lymphatic channel structures were maintained in the proper axillary lymph node, although sinus histiocytosis was detected. These results show that intranodal pressure in the proper axillary lymph node increases at early stages when metastatic tumor cells have not fully proliferated. Intranodal pressure may be a useful parameter for facilitating early diagnosis of lymph node metastasis.
A perfusion defect in metastatic lymph nodes (LNs) can be visualized as a localized area of low contrast on contrast-enhanced CT, MRI or ultrasound images. Hypotheses for perfusion defect include abnormal hemodynamics in neovascular vessels and decrease in blood flow in pre-existing blood vessels in the parenchyma due to compression of tumor growth in the LNs. However, the mechanism of perfusion defects in LNs during the early stage of LN metastasis has not yet been investigated. Here we show that the formation of a tumor mass with very few microvessels was associated with the development of a perfusion defect in the non-enlarged LN at the early stage of LN metastasis. We found in a mouse model of LN metastasis induced using non-keratinizing tumor cells that during formation of the perfusion defect in non-enlarged LN, the number of blood vessels £ 50 mm in diameter decreased, while the volume of existing blood vessels >50 mm in diameter increased using contrast-enhanced high-frequency ultrasound and contrast-enhanced micro-CT imaging systems with a maximum spatial resolution of > 30 mm. Furthermore, we found that tumor angiogenesis and pO2 changes in the metastatic LN were not observed. Our results demonstrate that the perfusion defect appear to be a specific form of tumorigenesis in the LN as vascular-rich organ at the early stage of metastasis. We anticipate a perfusion defect on ultrasound, CT or MRI images to be used as an indicator in the non-enlarged LN at the early stage of LN metastasis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.