Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice
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Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice. / Labitzky, Vera; Baranowsky, Anke; Maar, Hanna; Hanika, Sandra; Starzonek, Sarah; Ahlers, Ann-Kristin; Stübke, Katrin; Koziolek, Eva J; Heine, Markus; Schäfer, Paula; Windhorst, Sabine; Jücker, Manfred; Riecken, Kristoffer; Amling, Michael; Schinke, Thorsten; Schumacher, Udo; Valentiner, Ursula; Lange, Tobias.
in: CANCERS, Jahrgang 12, Nr. 2, 07.02.2020.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice
AU - Labitzky, Vera
AU - Baranowsky, Anke
AU - Maar, Hanna
AU - Hanika, Sandra
AU - Starzonek, Sarah
AU - Ahlers, Ann-Kristin
AU - Stübke, Katrin
AU - Koziolek, Eva J
AU - Heine, Markus
AU - Schäfer, Paula
AU - Windhorst, Sabine
AU - Jücker, Manfred
AU - Riecken, Kristoffer
AU - Amling, Michael
AU - Schinke, Thorsten
AU - Schumacher, Udo
AU - Valentiner, Ursula
AU - Lange, Tobias
PY - 2020/2/7
Y1 - 2020/2/7
N2 - 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 "metastasis" 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.
AB - 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 "metastasis" 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.
U2 - 10.3390/cancers12020385
DO - 10.3390/cancers12020385
M3 - SCORING: Journal article
C2 - 32046143
VL - 12
JO - CANCERS
JF - CANCERS
SN - 2072-6694
IS - 2
ER -