The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.

Laser speckle flowgraphy is a new method that enables the rapid evaluation of foot blood flow without contact with the skin. We used laser speckle flowgraphy to evaluate foot blood flow in peripheral arterial disease patients before and after surgical revascularization. A prospective single-center study. Thirty-one patients with 33 limbs that underwent surgical revascularization for peripheral arterial disease were included. Pre- and postoperative foot blood flows were measured on the plantar surface via laser speckle flowgraphy and skin perfusion pressure. The laser speckle flowgraphy device was used to visualize the blood flow distribution of the target skin and processed the pulse wave velocity of synchronized heart beats. The mean blood flow, which was expressed as the area of the pulse wave as the beat strength of skin perfusion on laser speckle flowgraphy converted into a numerical value, was assessed as dynamic changes following surgery. Beat strength of skin perfusion was also investigated in non-peripheral arterial disease controls (23 patients/46 limbs). The suitability of beat strength of skin perfusion in non-peripheral arterial disease controls was achieved; the beat strength of skin perfusion value was significantly higher in every area of interest in non-peripheral arterial disease controls compared to that in peripheral arterial disease limbs at the preoperative stage (105.8 ± 8.2 vs. 26.3 ± 8.2; P < 0.01). Although the pulse wave before surgery was visually flat in peripheral arterial disease patients, the pulse wave was remarkably and immediately improved through surgical revascularization. Beat strength of skin perfusion showed a dynamic change in foot blood flow (26.3 ± 8.2 at preoperation, 98.5 ± 6.7 immediately after surgery, 107.6 ± 5.7 at seven days after surgery, P < 0.01 for each compared to preoperation) that correlated with an improvement in skin perfusion pressure. Laser speckle flowgraphy is a noninvasive, contact-free modality that is easy to implement, and beat strength of skin perfusion is a useful indicator of foot circulation during the perioperative period. Further analysis with a larger number of cases is necessary to establish appropriate clinical use.

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.

Changes in extracellular matrix proteins may contribute significantly to the adaptation of vein grafts to the arterial circulation. We examined the production and distribution of versican and hyaluronan in intact human vein rings cultured ex vivo, veins perfused ex vivo, and cultured venous adventitial and smooth muscle cells. Immunohistochemistry revealed higher levels of versican in the intima/media compared to the adventitia, and no differences in hyaluronan. In the vasa vasorum, versican and hyaluronan associated with CD34⁺ progenitor cells. Culturing the vein rings for 14 days revealed increased versican immunostaining of 30–40% in all layers, with no changes in hyaluronan. Changes in versican accumulation appear to result from increased synthesis in the intima/media and decreased degradation in the adventitia as versican transcripts were increased in the intima/media, but unchanged in the adventitia, and versikine (the ADAMTS-mediated cleavage product of versican) was increased in the intima/media, but decreased in the adventitia. In perfused human veins, versican was specifically increased in the intima/media in the presence of venous pressure, but not with arterial pressure. Unexpectedly, cultured adventitial cells express and accumulate more versican and hyaluronan than smooth muscle cells. These data demonstrate a differential regulation of versican and hyaluronan in human venous adventitia vs. intima/media and suggest distinct functions for these extracellular matrix macromolecules in these venous wall compartments during the adaptive response of vein grafts to the arterial circulation.