Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice

Autor: Hanna Maar, Eva Jolanthe Koziolek, Markus Heine, Ann-Kristin Ahlers, Sabine Windhorst, Vera Labitzky, Thorsten Schinke, Udo Schumacher, Manfred Jücker, Paula Schäfer, Katrin Stübke, Ursula Valentiner, Tobias Lange, Sandra Hanika, Michael Amling, Sarah Starzonek, Kristoffer Riecken, Anke Baranowsky
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Volume 12
Issue 2
Cancers, Vol 12, Iss 2, p 385 (2020)
ISSN: 2072-6694
Popis: The majority of cancer-related deaths are due to hematogenous metastases, and the bone marrow (BM) represents one of the most frequent metastatic sites. To study BM metastasis formation in vivo, the most efficient approach is based on intracardiac injection of human tumor cells into immunodeficient mice. However, such a procedure circumvents the early steps of the metastatic cascade. Here we describe the development of xenograft mouse models (balb/c rag2-/- and severe combined immunodeficient (SCID)), in which BM metastases are spontaneously derived from subcutaneous (s.c.) primary tumors (PTs). As verified by histology, the described methodology including ex vivo bioluminescence imaging (BLI) even enabled the detection of micrometastases in the BM. Furthermore, we established sublines from xenograft primary tumors (PTs) and corresponding BM (BM) metastases using LAN-1 neuroblastoma xenografts as a first example. In vitro &ldquo
metastasis&rdquo
assays (viability, proliferation, transmigration, invasion, colony formation) partially indicated pro-metastatic features of the LAN-1-BM compared to the LAN-1-PT subline. Unexpectedly, after s.c. re-injection into mice, LAN-1-BM xenografts developed spontaneous BM metastases less frequently than LAN-1-PT xenografts. This study provides a novel methodologic approach for modelling the spontaneous metastatic cascade of human BM metastasis formation in mice. Moreover, our data indicate that putative bone-metastatic features get rapidly lost upon routine cell culture.
Databáze: OpenAIRE
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