BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.
Bone is the most common site of breast cancer metastasis. Although it is widely accepted that the microenvironment influences cancer cell behavior, little is known about breast cancer cell properties and behaviors within the native microenvironment of human bone tissue.We have developed approaches to track, quantify and modulate human breast cancer cells within the microenvironment of cultured human bone tissue fragments isolated from discarded femoral heads following total hip replacement surgeries. Using breast cancer cells engineered for luciferase and enhanced green fluorescent protein (EGFP) expression, we are able to reproducibly quantitate migration and proliferation patterns using bioluminescence imaging (BLI), track cell interactions within the bone fragments using fluorescence microscopy, and evaluate breast cells after colonization with flow cytometry. The key advantages of this model include: 1) a native, architecturally intact tissue microenvironment that includes relevant human cell types, and 2) direct access to the microenvironment, which facilitates rapid quantitative and qualitative monitoring and perturbation of breast and bone cell properties, behaviors and interactions. A primary limitation, at present, is the finite viability of the tissue fragments, which confines the window of study to short-term culture. Applications of the model system include studying the basic biology of breast cancer and other bone-seeking malignancies within the metastatic niche, and developing therapeutic strategies to effectively target breast cancer cells in bone tissues. Video LinkThe video component of this article can be found at
Background The Supplemental Nutrition Assistance Program (SNAP) expanded significantly after the Great Recession of 2008–2009, but no studies have characterized this new group of recipients. Few data sets provide details on whether an individual is a new or established recipient of SNAP. Objective We sought to identify new and existing SNAP recipients, and to examine differences in sociodemographic characteristics, health, nutritional status, and food purchasing behavior between new and existing recipients of SNAP after the recession. Methods We created a probabilistic algorithm to identify new and existing SNAP recipients using the 1999–2013 waves of the Panel Study of Income Dynamics. We applied this algorithm to the National Household Food Acquisition and Purchase Survey (FoodAPS), fielded during 2012–2013, to predict which individuals were likely to be new SNAP recipients. We then compared health and nutrition characteristics between new, existing, and never recipients of SNAP in FoodAPS. Results New adult SNAP recipients had higher socioeconomic status, better self-reported health, and greater food security relative to existing recipients, and were more likely to smoke relative to never recipients. New child SNAP recipients were less likely to eat all meals and had lower BMI relative to existing recipients. New SNAP households exhibited differences in food access and expenditures, although dietary quality was similar to that of existing SNAP households. Conclusion We developed a novel algorithm for predicting new and existing SNAP recipiency that can be applied to other data sets, and subsequently demonstrated differences in health characteristics between new and existing recipients. The expansion of SNAP since the Great Recession enrolled a population that differed from the existing SNAP population and that may benefit from different types of nutritional and health services than those traditionally offered.
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