Tumor‐associated lymphatic endothelial cell promotes invasion of cervical cancer cells

Abstract

The most common way for cervical cancer to spread is through the lymphatic system. Tumor-associated lymphatic endothelial cell (TLEC) has been considered to play a crucial role in metastasis of certain cancers. The aim of this study was to isolate TLEC from human cervical cancers and explore its involvement in metastasis-associated behaviors in vitro. Lymphatic vessels in 62 cervix tissue specimens ranging from cervical intraepithelial neoplasia (CIN) to advanced invasive cancer were detected using immunochemical staining with D2-40 antibody. Relation of lymphatic vessel density (LVD) to clinicopathological characters was analyzed. Primary TLECs were isolated by LYVE-1 immuno-magnetic beads from cervical cancer tissues and verified through expression of LEC markers Prox-1 and D2-40, and then cultured in vitro. Invasiveness and viability of cells were assessed by transwell assay and typan blue exclusion, respectively. Our results showed that higher LVD was significantly associated with advanced FIGO stage, pelvic lymphatic nodal metastasis (LNM), and poorer cell differentiation. TLECs were successfully primarily isolated and cultured in vitro. Supernatant of TLEC enhanced invasiveness of Hela cell, but did not significantly affect cell viability. In conclusion, TLECs might actively promote lymphatic metastasis of cervical cancer. Further studies are needed to demonstrate the underlying mechanisms.

Microfluidic Tumor–Vascular Model to Study Breast Cancer Cell Invasion and Intravasation

“…In Our working model is that the crosstalk between tumor and endothelial cells are crucial during cancer progression, namely invasion and intravasation. We know from previous studies that endothelial cells affect tumor cell behavior with respect to morphology and the invasive characteristics [23] and in turn the cancer cells secrete several biochemical factors which modify the vascular network morphology, which facilitates tumor cell intravasation [6a], [24] . Consistent to these studies, our findings showed that significantly higher number of cancer cells invaded the stromal region in the presence of endothelial vascular networks.…”

Improved computer-assisted analysis of the global lymphatic network in human cervical tissues

“…Subsequent immunohistochemical studies on cervical neoplasms confirmed a positive association between lymphatic vessel density and lymph node metastases. 14,[16][17][18][19][20][21] Taken together, these results suggest an early lymphangiogenesis switch with an increased risk of lymphatic dissemination during cancer progression that could be assessed by lymphatic vessel density quantification. However, until recently, lymphatic vessel density quantification has relied on the hot spot technique previously criticized for its subjectivity.…”

“…Especially, most clinical studies showed that peritumoral lymphatic vessel density is associated with an aggressiveness behavior and appeared as a strong predictive factor of lymph node metastasis. [14][15][16][17][18][19][20][21]36 However, contradictory results were reported by three others groups. 10,23,24 Interestingly, a few years ago, Van der Auwera et al 22 proposed that these discrepancies are caused by a lack of reproducibility when lymphatic vessel density is measured by the conventional optical microscopy (hot spot technique).…”

The Role of PROX1 in Neoplasia: A Key Player Often Overlooked

“…cervical cancer tissues do actively promote lymphatic metastasis. PROX1 served as a diagnostic marker for tumor-associated lymphatic endothelial cells [59].…”

“…Moreover, in vitro cultures showed that tumor-associated lymphatic endothelial cells from cervical cancer tissues do actively promote lymphatic metastasis. PROX1 served as a diagnostic marker for tumor-associated lymphatic endothelial cells [ 59 ].…”