Abstract
Adhesion is critical for the maintenance of cellular structures as well as intercellular communication, and its dysfunction occurs prevalently during cancer progression. Recently, a growing number of studies indicated the ability of oxygen to regulate adhesion molecules expression, however, the influence of physiological hypoxia (physioxia) on cell adhesion remains elusive. Thus, here we aimed: (i) to develop an optical tweezers based assay to precisely evaluate single diffuse large B-cell lymphoma (DLBCL) cell adhesion to neighbor cells (mesenchymal stromal cells) and extracellular matrix (Matrigel) under normoxia and physioxia; and, (ii) to explore the role of integrins in adhesion of single lymphoma cell. We identified the pronouncedly reduced adhesive properties of lymphoma cell lines and primary lymphocytes B under physioxia to both stromal cells and Matrigel. Corresponding effects were shown in bulk adhesion assays. Then we emphasized that impaired β1, β2 integrins, and cadherin-2 expression, studied by confocal microscopy, account for reduction in lymphocyte adhesion in physioxia. Additionally, the blockade studies conducted with anti-integrin antibodies have revealed the critical role of integrins in lymphoma adhesion. To summarize, the presented approach allows for precise confirmation of the changes in single cell adhesion properties provoked by physiological hypoxia. Thus, our findings reveal an unprecedented role of using physiologically relevant oxygen conditioning and single cell adhesion approaches when investigating tumor adhesion in vitro.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas (NHL) and it constitutes approximately a third of all NHL [1]
In vitro growth data suggests that the effect of physioxic and hypoxic treatment on diffuse large B-cell lymphoma (DLBCL) proliferation strickly depends on the lymphoma cell type
We introduced an optical tweezers technology for testing single B-cell interactions with stromal cell and extracellular matrix in normoxia and physioxia
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas (NHL) and it constitutes approximately a third of all NHL [1]. Common features of NHLs is the bone marrow involvement, for DLBCL it concerns up to 40% of cases [2]. Accumulating evidences confirm the critical role of cellular interactions between cancer cells and bone marrow or/and lymphatic tissue microenvironments in lymphoma growth, chemoresistance [3], and survival [4] through a combination of adhesion molecules, chemokines, and cytokines [5,6,7,8]. The oxygen-related changes in the early adhesion of the primary lymphocytes B in the context of a living cells in their microenvironment have been explored
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