Abstract
Bone metastasis is a lethal and incurable disease. It is the result of the dissemination of cancer cells to the bone marrow. Due to the difficulty in sampling and detection, few techniques exist to efficiently and consistently detect and quantify disseminated tumor cells (DTCs) in the bone marrow of cancer patients. Because mouse models represent a crucial tool with which to study cancer metastasis, we developed a novel method for the simple selection-free detection and quantification of bone marrow DTCs in mice. We have used this protocol to detect human and murine DTCs in xenograft, syngeneic, and genetically engineered mouse models. We are able to detect and quantify bone marrow DTCs in mice that do not have overt bone metastasis. This protocol is amenable not only for detection and quantification purposes but also to study the expression of markers of numerous biological processes or tissue-specificity.
Highlights
Bone metastasis leads to approximately 280,000– 350,000 cancer-related deaths in the United States each year [1, 2]
Bone metastasis occurs through a complex cascade of events that results in circulating tumor cells (CTCs) from the blood extravasating and invading the bone marrow – these cells within the bone marrow are referred to as disseminated tumor cells (DTCs) [4]
This method may result in loss of cancer cells from the sample, as some CTCs are inadvertently removed during the depletion step
Summary
Bone metastasis leads to approximately 280,000– 350,000 cancer-related deaths in the United States each year [1, 2]. DTCs occupy the hematopoietic stem cell niche within the bone marrow [5], often remaining dormant for years before becoming reactivated, leading to cancer recurrence [6]. Beyond single DTCs, death from bone metastasis may be due to dissemination of disease via metastatic re-seeding from other secondary sites [7, 8]. Metastatic sites may re-seed primary tumors in a multi-directional fashion [8]. These important and unanswered biological questions about bone marrow DTCs and the metastatic process underscore the need for efficient and consistent methods for DTC detection in model systems
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