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 |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research lcsh:RC254-282 xenograft mouse model Article Metastasis 03 medical and health sciences 0302 clinical medicine In vivo Neuroblastoma Medicine Bioluminescence imaging business.industry Bone metastasis bioluminescence imaging lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Bone marrow business Ex vivo spontaneous bone marrow metastasis |
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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