Delimiting CD34+ Stromal Cells/Telocytes Are Resident Mesenchymal Cells That Participate in Neovessel Formation in Skin Kaposi Sarcoma

Abstract

Kaposi sarcoma (KS) is an angioproliferative lesion in which two main KS cell sources are currently sustained: endothelial cells (ECs) and mesenchymal/stromal cells. Our objective is to establish the tissue location, characteristics and transdifferentiation steps to the KS cells of the latter. For this purpose, we studied specimens of 49 cases of cutaneous KS using immunochemistry and confocal and electron microscopy. The results showed that delimiting CD34+ stromal cells/Telocytes (CD34+SCs/TCs) in the external layer of the pre-existing blood vessels and around skin appendages form small convergent lumens, express markers for ECs of blood and lymphatic vessels, share ultrastructural characteristics with ECs and participate in the origin of two main types of neovessels, the evolution of which gives rise to lymphangiomatous or spindle-cell patterns—the substrate of the main KS histopathological variants. Intraluminal folds and pillars (papillae) are formed in the neovessels, which suggests they increase by vessel splitting (intussusceptive angiogenesis and intussusceptive lymphangiogenesis). In conclusion, delimiting CD34+SCs/TCs are mesenchymal/stromal cells that can transdifferentiate into KS ECs, participating in the formation of two types of neovessels. The subsequent growth of the latter involves intussusceptive mechanisms, originating several KS variants. These findings are of histogenic, clinical and therapeutic interest.

Tumor-associated telocytes

“…Besides, these particular stromal cells (CD34 + SCs/TCs) were testified to be associated with the neovessel formation in the skin Kaposi sarcoma, which was classified as a sort of distinct viral and immunologically related malignant neoplasm. [ 21 ] This valuable finding substantiated that CD34 + SCs/TCs delimited the Kaposi sarcoma margin and non-affected pre-existing blood veins through their elongated Tps. Moreover, CD34 + SCs/TCs were initially observed to establish extensive communications with inflammatory cells that were positively pigmented by CD45, evidencing the conception that TATCs could create a three-dimension interactive network and maintain close-knit inter-associations with intricate signaling information in the TME.…”

Phenomena of Intussusceptive Angiogenesis and Intussusceptive Lymphangiogenesis in Blood and Lymphatic Vessel Tumors

“…Examples of low-grade malignancy encompassed retiform hemangioendothelioma (n: 2) and papillary intralymphatic angioendothelioma or Dabska tumor (n: 1), while malignant tumors comprised angiosarcoma (n: 5) and Kaposi sarcoma (n: 5). From our previous studies in some vessel tumors, we randomly obtained cases of intravascular papillary endothelial hyperplasia [27], sinusoidal hemangioma [28], lymphatic malformations/lymphangiomas [29], and angiolipoma [32], selecting those of rapid evolution in lobular capillary hemangioma [30] and early stages in Kaposi sarcoma [33]. Ethical approval for this study was obtained from the Ethics Committee of La Laguna University [Comité de Ética de la Investigación y de Bienestar Animal, CEIBA 2023-3343], including the dissociation of the samples from any information that could identify the patient.…”

Telocytes and inflammation: A review

“…[27,57] In addition, normalization of TC numbers is associated with disease remission and is involved in the process of skin tissue repair and revascularization. [58,59] In a rat experiment on myocardial infarction, TCs were found to inhibit myocardial microvascular endothelial cell apoptosis by targeting Cdip1 silencing through exosomal miR-21-5p to inhibit myocardial infarction angiogenesis. [60,61] In addition to affecting angiogenesis, TCs show strong immunoreactivity toward APG5, transforming growth factor beta and nuclear factor erythroid-2-related factor 2; affect phagocytosis and autophagy; and may also be involved in cell differentiation and regeneration.…”