Malignant pleural mesothelioma nodules remodel their surroundings to vascularize and grow
Year: 2022
Type: article
Abstract: Background: The microanatomical steps of malignant pleural mesothelioma (MPM) vascularization and the resistance mechanisms to anti-angiogenic drugs in MPM are unclear. Methods: . Results: . In co-cultures of MPM and endothelial cells, P31 spheroids permitted endothelial sprouting (ES) with minimal spatial distortion, whereas SPC111 spheroids repealed endothelial sprouts. Both MPM lines induced the early onset of submesothelial microvascular plexuses covering large pleural areas including regions distant from tumor colonies. The development of these microvascular networks occurred due to both intussusceptive angiogenesis (IA) and ES and was accelerated by vascular endothelial growth factor A (VEGF-A)-overexpression. Notably, SPC111 colonies showed different behavior to P31 cells. P31 nodules incorporated tumor-induced capillary plexuses from the earliest stages of tumor formation. P31 cells deposited a collagenous matrix of human origin which provided "space" for further intratumoral angiogenesis. In contrast, SPC111 colonies pushed the capillary plexuses away and thus remained avascular for weeks. The key event in SPC111 vascularization was the development of a desmoplastic matrix of mouse origin. Continuously invaded by SPC111 cells, this matrix transformed into intratumoral connective tissue trunks, providing a route for ES from the diaphragm. Conclusions: Here, we report two distinct growth patterns of orthotopically implanted human MPM xenografts. In the invasive pattern, MPM cells invade and thus co-opt peritumoral capillary plexuses. In the pushing/desmoplastic pattern, MPM cells induce a desmoplastic response within the underlying tissue which allows the ingrowth of a nutritive vasculature from the pleura.
DOI: 10.21037/tlcr-21-828
Authors: Ildiko Kovacs, Edina Bugyik, Katalin Dezso, Julia Tarnoki-Zach, Elod Mehes, Marton Gulyas, Andras Czirok, Elisabeth Lang, Michael Grusch, Karin Schelch, Balazs Hegedus, Ildiko Horvath, Nandor Barany, Zsolt Megyesfalvi, Anna Tisza, Zoltan Lohinai, Mir Alireza Hoda, Konrad Hoetzenecker, Francesco Pezzella, Sandor Paku, Viktoria Laszlo, Balazs Dome
Institutions: Országos Korányi Tbc és Pulmonológiai Intézet, Semmelweis University, Eötvös Loránd University, University of Kansas Medical Center, Medical University of Vienna, Ruhrlandklinik, Essen University Hospital, Stiftung Universitätsmedizin Essen, National Institute of Oncology, John Radcliffe Hospital, University of Oxford
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4285502997