A systematic review of how social connectedness influences associations between racism and discrimination on health outcomes.

Racial discrimination is a well-known risk factor of racial disparities in health. Although progress has been made in identifying multiple levels through which racism and racial discrimination influences health, less is known about social factors that may buffer racism's associations with health. We conducted a systematic review of the literature with a specific focus on social connectedness, racism, and health, retrieving studies conducted in the United States and published between January 1, 2012, and July 30, 2022, in peer-reviewed journals. Of the 787 articles screened, 32 were selected for full-text synthesis. Most studies (72%) were at the individual level, cross-sectional, and among community/neighborhood, school, or university samples. Studies had good methodological rigor and low risk of bias. Measures of racism and racial discrimination varied. Discrimination scales included unfair treatment because of race, schedule of racist events, experiences of lifetime discrimination, and everyday discrimination. Measures of social connectedness (or disconnectedness) varied. Social-connectedness constructs included social isolation, loneliness, and social support. Mental health was the most frequently examined outcome (75%). Effect modification was used in 56% of studies and mediation in 34% of studies. In 81% of studies, at least 1 aspect of social connectedness significantly buffered or mediated the associations between racism and health. Negative health associations were often weaker among people with higher social connectedness. Social connectedness is an important buffering mechanism to mitigate the associations between racial discrimination and health. In future studies, harmonizing metrics of social connectedness and racial discrimination can strengthen causal claims to inform interventions.

N-cadherin in osteolineage cells modulates stromal support of tumor growth.

Tumor growth and metastases are dependent on interactions between cancer cells and the local environment. Expression of the cell-cell adhesion molecule N-cadherin (Ncad) is associated with highly aggressive cancers, and its expression by osteogenic cells has been proposed to provide a molecular "dock" for disseminated tumor cells to establish in pre-metastatic niches within the bone. To test this biologic model, we conditionally deleted the Ncad gene (Cdh2) in osteolineage cells using Osx-cre (cKO). Contrary to expectations, the metastatic breast cancer cell line PyMT-BO1 was able to form tumors in bone and to induce osteolysis in cKO as well as in control mice. Despite absence of Ncad, bone marrow stromal cells isolated from cKO mice were able to engage in direct cell-cell interactions with tumor cells expressing either N- or E-cadherin. However, subcutaneous PyMT-BO1 and B16F10 tumors grew larger in cKO relative to control littermates. Cell tracking experiments using the Ai9 reporter revealed the presence of Osx+ and Ncad+ cells in the stroma of extra-skeletal tumors and in a small population of lung cells. Gene expression analysis by RNAseq of Osx+ cells isolated from extra-skeletal tumors revealed alterations of pro-tumorigenic signaling pathways in cKO cells relative to control Osx+ cells. Thus, Ncad in Osx+ cells is not necessary for the establishment of bone metastases, but in extra-skeletal tumors it regulates pro-tumorigenic support by the microenvironment.