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

Standard

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, Vol. 12, No. 2, 07.02.2020.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

APA

Vancouver

Bibtex

@article{4ab9018526da4467917a4b72f593d631,
title = "Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice",
abstract = "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.",
author = "Vera Labitzky and Anke Baranowsky and Hanna Maar and Sandra Hanika and Sarah Starzonek and Ann-Kristin Ahlers and Katrin St{\"u}bke and Koziolek, {Eva J} and Markus Heine and Paula Sch{\"a}fer and Sabine Windhorst and Manfred J{\"u}cker and Kristoffer Riecken and Michael Amling and Thorsten Schinke and Udo Schumacher and Ursula Valentiner and Tobias Lange",
year = "2020",
month = feb,
day = "7",
doi = "10.3390/cancers12020385",
language = "English",
volume = "12",
journal = "CANCERS",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",

}

RIS

TY - JOUR

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 -