Leibert Pub: Zebrafish Tumor Graft Transplantation to Grow Tumors In Vivo That Engraft Poorly as Single Cell Suspensions (Ignatius Lab)

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Abstract

Angiosarcoma is a clinically aggressive tumor with a high rate of mortality. It can arise in vascular or lymphatic tissues, involve any part of the body, and aggressively spread locally or metastasize. Angiosarcomas spontaneously develop in the tp53 deleted (tp53del/del) zebrafish mutant. However, established protocols for tumor dissection and transplantation of single-cell suspensions of angiosarcoma tumors result in inferior implantation rates. To resolve these complications, we developed a new tumor grafting technique for engraftment of angiosarcoma and similar tumors in zebrafish, which maintains the tumor microenvironment and has superior rates of engraftment.

Zebrafish tumor models have provided unique and complementary ways to study cancer biology in vivo.1 For example, zebrafish that are completely deficient or harbor a loss-of-function mutation in the tp53 tumor suppressor gene spontaneously develop a spectrum of tumors, including malignant peripheral nerve sheath tumors (MPNSTs), leukemias, angiosarcomas, and germ cell tumors.2–4 It is notable that these tumors were shown to molecularly and histologically resemble human cancers.2–4 Furthermore, the use of syngeneic animals (CG1 strain) enables studies involving tumor cell transplantation into recipient zebrafish with an intact immune system.5,6 Traditionally, tumor cells are transplanted in zebrafish as single-cell suspensions admixed with supporting cells or in cell culture media/matrix.7–11 However, we find that for angiosarcomas, and possibly other rare tumors, single-cell dissociation methods are not optimal for tumor engraftment. In this study, we describe tumor graft transplantation as an alternate superior method for angiosarcoma tumor engraftment.

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Article Categories: Research Paper