Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

Abstract

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma

“…In concert with primary tumors, our study identifies immune suppressive molecules in tumor-draining LNs, suggesting that immune mechanisms operating in metastatic LNs 25 , 37 , 61 , 62 may at least in part be similar to those in primary tumors. 63 In contrast to primary tumors, we found a significant correlation between LECs and FoxP3 + lymphocytes.…”

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

“…Previous studies have also identified that the decrease in NCOA5 expression in esophageal squamous cell carcinoma (ESCC) tissue is associated with the differentiation status of the tumor and the TNM stage, while is not associated with age, sex, weight loss, tumor location or lymph node metastasis (26,27). In addition, the expression of NCOA5 in normal tissues was higher compared with that in tumor tissues.…”

Tipping Tumor Microenvironment against Drug Resistance

“…While VEGFA-VEGFR2 axis signaling mainly induces cancer blood vessel (BV) angiogenesis, VEGFC/D-VEGFR3 pathway activity usually promotes tumor lymphatic vessel (LV) angiogenesis (lymph-angiogenesis) [14]. In addition to providing blood supply for tumor growth and facilitating cancer spreading, local endothelial cells (EC) also directly function as a pro-survival player against apoptosis of cancer cells because VEGF and VEGFR are expressed by both EC and tumor cells [11,15].…”

“…On the other hand, lymphatic endothelium secrets CXCL12 and CCL21 chemokines which recruit the responding receptor CXCR4-or CCR7-expressing cancer cells through chemo-attraction, thereby promoting malignant cell migration and metastasis [14]. It is thus not surprising that VEGF-VEGFR-mediated cancer cell-EC interactions have been reported to contribute to chemo-therapy resistance in several tumor types including lungcolon cancer and soft tissue sarcoma [11,13].…”