Experimental models to study lymphatic and blood vascular metastasis

Abstract

As a model system for the understanding of human cancer, the mouse has proved immensely valuable. Indeed, studies of mouse models have helped to define the nature of cancer as a genetic disease and demonstrated the causal role of genetic events found in tumors. As an experimental platform, they have provided critical insight into the process of tumor metastasis in the lymphovascular system. Once viewed with skepticism, mouse models are now an integral arm of basic and clinical cancer research. The use of a genetically tractable organism that shares organ systems and an immense degree of genetic similarity to humans provides a means to examine multiple features of human disease. Mouse models enable development and testing of new approaches to disease prevention and treatment, identification of early diagnostic markers and novel therapeutic targets, and an understanding of the in vivo biology and genetics of tumor initiation, promotion, progression, and metastasis. This review summarizes recent mouse models for lymphangiogenesis and the process of lymphovascular metastasis, focusing on the use of the cornea as an experimental platform for lymphangiogenesis in inflammation and immunity, and on the use of molecular and viral vector mediated imaging and to identify and monitor lymph node metastases of prostate cancer.

Protective effects of matrix metalloproteinase-12 following corneal injury

“…Lymphatic vessels are not usually present in the cornea, but corneal injury can result in lymphangiogenesis (Chen et al, 2011;Cursiefen et al, 2003). We stained flat mounts with the lymphatic vessel marker LYVE-1 to assess corneal lymphangiogenesis 7 days after injury (Fig.…”

Live imaging of newly formed lymphatic vessels in the cornea

“…Though lymphatic dysfunction has been found in a broad spectrum of disorders from transplant rejection to cancer metastasis, to date, there is still little effective treatment for lymphatic diseases, so it is a field with urgent demand for new experimental approaches and therapeutic protocols. The cornea provides an ideal site for lymphatic research due to its accessible location, transparent nature, and alymphatic status under normal condition [2,4]. Indeed, the use of this tissue for tumor angiogenesis research dates back to 1970s [5].…”

“…For example, mouse strains with specific fluorescent reporters for dendritic cells, macrophages, or nerve fibers may be used in combination with this new technology to advance our research goals in the related fields. It is also possible to employ this new technology to examine lymphatic processes induced by other biological or pathological insults, such as growth factors, infections, tumors, trauma, transplantation, or chemical burn, of which various models have been developed in mouse cornea [4].…”

Watching lymphatic vessels grow by making them glow

“…It has several attractive features including a reproducible time course of sprouting lymphangiogenesis into a tissue not normally endowed with lymphatics, the ability to test growth factors or therapeutic compounds by implantation of slow release micropellets, and the capability to perform transplantation surgeries to test lymphatic involvement in the graft-rejection response [2]. Its value was recently demonstrated in a seminal study by Albuquerque and colleagues where a new endogenous inhibitor of lymphatic vessel formation was discovered [3].…”