Antibody panel used for multiplexed antibody-based imaging of Human Pancreas Analysis Program (HPAP) samples by CODEX

<p>This data file details antibodies applied to human pancreas tissue samples from the Human Pancreas Analysis Program (HPAP; RRID:SCR_016202) of the <a href="https://hirnetwork.org/">Human Islet Research Network</a> (HIRN; RRID:SCR_014393). Images will be uploaded for interactive analysis on <a href="https://pancreatlas.org/datasets">Pancreatlas</a> (RRID:SCR_018567) and made available for download via <a href="https://hpap.pmacs.upenn.edu/">PANC-DB</a>. Workflow is documented on protocols.io: <a href="https://dx.doi.org/10.17504/protocols.io.36wgq7dryvk5/v1">dx.doi.org/10.17504/protocols.io.36wgq7dryvk5/v1</a>.</p><p>Table format adapted from Radtke AJ, Quardokus EM, Saunders DC (2022), <a href="https://doi.org/10.5281/zenodo.7386417">SOP: Construction of Organ Mapping Antibody Panels for Multiplexed Antibody-Based Imaging of Human Tissues</a>. See also: Saunders D; Reihsmann R. <a href="https://doi.org/10.48539/HBM754.BHVR.258">OMAP-13: Organ Mapping Antibody Panel (OMAP) for Multiplexed Antibody-Based Imaging of Human Pancreas with CODEX, v1.0</a>.</p&gt

Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion through differential proteolysis

While many adhesion receptors are known to influence tumor progression, the mechanisms by which they dynamically regulate cell-cell adhesion remain elusive. We previously identified Activated Leukocyte Cell Adhesion Molecule (ALCAM) as a clinically relevant driver of metastasis and hypothesized that a tunable mechanism of ectodomain shedding regulates its contribution to dissemination. To test this hypothesis, we examined an under-explored ALCAM splice variant (ALCAM-Iso2) and demonstrated that loss of the membrane-proximal region of ALCAM (exon 13) increased metastasis four-fold. Mechanistic studies identified a novel MMP14-dependent membrane distal cleavage site in ALCAM-Iso2, which mediated a ten-fold increase in shedding, thereby decreasing cellular cohesion. Importantly, the loss of cohesion is not limited to the cell capable of shedding because the released extracellular domain diminished cohesion of non-shedding cells through disruption of ALCAM-ALCAM interactions. ALCAM-Iso2-dominated expression in bladder cancer tissue, compared to normal bladder, further emphasizes that ALCAM alternative splicing may contribute to clinical disease progression. The requirement for both the loss of exon 13 and the gain of metalloprotease activity suggests that ALCAM shedding and concomitant regulation of tumor cell adhesion is a locally tunable process