Abstract
Disseminated tumor cells in the bone marrow environment are the main cause of systemic metastasis after curative treatment for major solid tumors. However, the detailed biological processes of tumor biology in bone marrow have not been well defined in a real-time manner, because of a lack of a proper in vivo experimental model thereof. In this study, we established intravital imaging models of the bone marrow environment to enable real-time observation of cancer cells in the bone marrow. Using these novel imaging models of intact bone marrow and transplanted bone marrow of mice, respectively, via two-photon microscopy, we could first successfully track and analyze both the distribution and the phenotype of cancer cells in bone marrow of live mouse. Therefore, these novel in vivo imaging models for the bone marrow would provide a valuable tool to identify the biologic processes of cancer cells in a real-time manner in a live animal model.
Highlights
Systemic metastasis is a major feature of major cancers even after margin-negative resection of a primary cancer lesion (1, 2)
Human cancer cell lines MCF7 and AsPC-1 were obtained from the American Tissue Culture Collection (ATCC) and grown in RPMI-1640 medium (ThermoFisher, Waltham, MA, USA) supplemented with 10% fetal bovine serum, 100 U/ml penicillin, and 100 μg/ml streptomycin
These cell lines were authenticated by standard short tandem repeat DNA typing methodology before purchase from the ATCC
Summary
Systemic metastasis is a major feature of major cancers even after margin-negative resection of a primary cancer lesion (1, 2). Circulating tumor cells derived from primary cancer lesion can be disseminated to secondary organs including bone marrow blood, lymph node, and distant organ via blood vessels or lymphatic channels and can cause early systemic recurrence regardless of definite treatment (3, 4). The mechanism of an awakening or activation of cancer cells in secondary organs should be investigated in order to prevent early systemic metastasis even in resectable cancer. The tumor biology of cancer cells in the bone marrow environment, the main site of minimal residual disease after curative cancer treatment, should be investigated in order to identify the specific process of systemic metastasis in most solid cancers (3, 10, 11). The lack of an in vivo experimental model for cancer cells in the bone marrow environment has been a major barrier to exploring the initial process of systemic metastasis (4, 12, 13). The aim of this study is to establish intravital imaging model of cancer cells in the bone marrow environment
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