{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:59:44Z","timestamp":1772006384020,"version":"3.50.1"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Aggregation and adhesion of ovarian cancer cells are facilitated by integrins, key adhesion receptors in ovarian cancer. Here we identify changes in the expression of integrins (ITG), their ligands and regulators during ovarian cancer progression and metastatic dissemination that allow for the adaptation of the cellular phenotype to aggregation and adhesion and promote cancer cell survival and metastatic outgrowth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We mimicked the stages of peritoneal dissemination of ovarian metastases by using benign cells and ovarian cancer cells representing slow- and fast developing disease and generated adherent, spheroid, and adherent-spheroid mouse ovarian surface epithelial cultures adjusted for oxygen and glucose levels as reported for malignant ascites. We determined changes in integrin expression, other adhesion receptors, ECM proteins and their regulators by qPCR RT2 PCR arrays and Western blotting. Spatial and intracellular protein expression in 3D spheroids was determined by confocal microscopy and quantitated by IMARIS software. Relevance of specific integrins for aggregation, adherence, and outgrowth was determined using specific inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Small changes in the highly expressed\n                      <jats:italic>ITG\u03b13, ITG\u03b15, ITG\u03b1V<\/jats:italic>\n                      , and\n                      <jats:italic>ITG\u03b21<\/jats:italic>\n                      after aggregation in concert with elevated ITG\u03b14 and ITG\u03b15 expression suggested changes in integrin heterodimer composition that support aggregation. 3D spatial analysis of adherent spheroids revealed high expression of ITG\u03b12, ITG\u03b1V, and ITG\u03b21 at the adhesion sites, while ITG\u03b13 was predominantly expressed in the spheroid periphery. This was not correlated to their distinct spatial expression patterns in spheroids (uniformly expressed or higher at the periphery). Importantly, most integrins and CD44 were localized in the nucleus where they potentially can affect gene transcription. Only the inhibition of ITG\u03b1V\u03b21 and ITG\u03b12\u03b21 effectively suppressed spheroid adhesion and outgrowth, highlighting their importance as stage-specific target to block peritoneal metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our studies show that integrin expression and localization are dynamic, spatially regulated, and functionally compartmentalized during ovarian cancer progression and dissemination. The coordinated upregulation of integrins, other adhesion molecules (CD44, NCAM1, VCAM), ECM (FN1, collagens) and their regulators (SPP1, TIMP2,3) in response to the culture conditions indicate a complex reprogramming of adhesion networks that can facilitate different steps of ovarian cancer progression and dissemination. Nuclear localization of integrins and CD44 point to dual roles in adhesion, survival, and proliferation by activating adhesion-mediated signaling pathways and directly affect gene transcription that support a switch from a more dormant phenotype to active proliferation and invasion after adhesion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1744403","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:03:31Z","timestamp":1772003011000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic integrin expression, atypical nuclear localization, and spatial distribution during ovarian cancer progression and metastasis"],"prefix":"10.3389","volume":"14","author":[{"given":"Nazia","family":"Bano","sequence":"first","affiliation":[{"name":"Translational Biology, Medicine and Health, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack L.","family":"Browning","sequence":"additional","affiliation":[{"name":"School of Neuroscience, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods and Exercise, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malaika","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Biology, Hollins University","place":["Roanoke, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piper","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Statistics, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Statistics, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva M.","family":"Schmelz","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods and Exercise, Virginia Tech","place":["Blacksburg, VA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2014.07.013","article-title":"Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis","volume":"158","author":"Aceto","year":"2014","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1093\/carcin\/23.2.237","article-title":"Overexpression of alpha(v)beta6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade","volume":"23","author":"Ahmed","year":"2002","journal-title":"Carcinogenesis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s10585-005-1262-y","article-title":"Role of integrin receptors for fibronectin, collagen and laminin in the regulation of ovarian carcinoma functions in response to a matrix microenvironment","volume":"22","author":"Ahmed","year":"2005","journal-title":"Clin. 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