The Tumor Vessel Targeting Strategy: A Double-Edged Sword in Tumor Metastasis

Tumor vessels provide essential paths for tumor cells to escape from the primary tumor and form metastatic foci in distant organs. The vessel targeting strategy has been widely used as an important clinical cancer chemotherapeutic strategy for patients with metastatic tumors. Our review introduces the contribution of angiogenesis to tumor metastasis and summarizes the application of Food and Drug Administration (FDA)-approved vessel targeting drugs for metastatic tumors. We recommend the application and mechanisms of vascular targeting drugs for inhibiting tumor metastasis and discuss the risk and corresponding countermeasures after vessel targeting treatment.

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Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

Marine Drugs ◽

10.3390/md17070415 ◽

2019 ◽

Vol 17 (7) ◽

pp. 415 ◽

Cited By ~ 2

Author(s):

Bolin Jing ◽

Gong Cheng ◽

Jianjun Li ◽

Zhuo A. Wang ◽

Yuguang Du

Keyword(s):

Tumor Cells ◽

Liver Tumor ◽

Hepg2 Cells ◽

Tumor Metastasis ◽

Inhibitory Effect ◽

Chitosan Oligosaccharide ◽

Inhibitory Effects ◽

Tumor Vessel ◽

Destructive Effect ◽

Cell Metastasis

Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage(s) of tumor metastasis COS targeted. To study the inhibitory effects of a new partially acetylated chitooligosaccharide (paCOS) with fraction of acetylation (FA) 0.46 on each phase of liver cancer cell metastasis, a dynamic tumor-vessel microsystem undergoing physiological flow was leveraged. paCOS (FA = 0.46) significantly inhibited proliferation of HepG2 cells through vascular absorption on the chip, and inhibited migration of HepG2 cells by inhibiting the formation of pseudopod in liver tumor cells. It was also found that paCOS at 10 μg/mL had a stronger inhibitory effect on liver tumor cells invading blood vessels than that of paCOS at 100 μg/mL, and paCOS at 100 μg/mL, which had a significant destructive effect on tumor vascular growth and barrier function. Moreover, paCOS reduced the number of liver tumor cells adhering onto the surface of HUVECs layer after 3 h of treatment. Therefore, the results revealed that paCOS had considerable potential as drugs for anti-tumor metastasis.

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Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Science ◽

10.1126/science.aav0173 ◽

2019 ◽

Vol 363 (6427) ◽

pp. 644-649 ◽

Cited By ~ 59

Author(s):

Choong-kun Lee ◽

Seung-hwan Jeong ◽

Cholsoon Jang ◽

Hosung Bae ◽

Yoo Hyung Kim ◽

...

Keyword(s):

Lymph Nodes ◽

Bile Acids ◽

Tumor Cells ◽

Tumor Metastasis ◽

Metabolic Adaptation ◽

Acid Oxidation ◽

Transcriptional Coactivator ◽

Metastatic Tumors ◽

Genetic Ablation ◽

Receptor Inhibition

In cancer patients, metastasis of tumors to sentinel lymph nodes (LNs) predicts disease progression and often guides treatment decisions. The mechanisms underlying tumor LN metastasis are poorly understood. By using comparative transcriptomics and metabolomics analyses of primary and LN-metastatic tumors in mice, we found that LN metastasis requires that tumor cells undergo a metabolic shift toward fatty acid oxidation (FAO). Transcriptional coactivator yes-associated protein (YAP) is selectively activated in LN-metastatic tumors, leading to the up-regulation of genes in the FAO signaling pathway. Pharmacological inhibition of FAO or genetic ablation of YAP suppressed LN metastasis in mice. Several bioactive bile acids accumulated to high levels in the metastatic LNs, and these bile acids activated YAP in tumor cells, likely through the nuclear vitamin D receptor. Inhibition of FAO or YAP may merit exploration as a potential therapeutic strategy for mitigating tumor metastasis to LNs.

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MHC Class 1 and PDL-1 Status of Primary Tumor and Lymph Node Metastatic Tumor Tissue in Gastric Cancers

Gastroenterology Research and Practice ◽

10.1155/2019/4785098 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Ibrahim Halil Erdogdu

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Cancer Cells ◽

Tumor Cells ◽

Primary Tumor ◽

Tumor Tissue ◽

Metastatic Tumor ◽

Tumor Escape ◽

Metastatic Tumors ◽

Primary Tumors

The prognosis of metastatic gastric cancer is poor. Despite the use of VEGF-, EGFR-, and HER2-targeting agents, prognosis is still poor in advanced gastric cancer. Although cancer immunotherapy responds well in some patients, clinical use is limited due to unanswered patients. For this reason, it is necessary to know the characteristics of primary and metastatic cancer cells for patient selection for immunotherapy and additional criteria are required. MHC-1 downregulation is most frequently observed in the tumor escape mechanism of cancer cells from the immune system. MHC-1 downregulation with increased PDL-1 expression of cancer cells has an important role in immune escape. MHC-1 downregulation and PDL-1 expression have been shown in many types of cancers. However, there is no study on the status of MHC-1 and PDL-1 in primary and metastatic tumor tissue. In this study, MHC-1 and PDL-1 score in primary and metastatic tumor cells was evaluated in 43 gastric cancer patients with lymph node metastasis. According to our results, the primary tumor PDL-1 score was correlated with the number of metastatic lymph nodes (r=0.258; p=0.024) and primary tumor size (r=0.341; p=0.045). A similar correlation was found between the primary tumor PDL-1 score and the metastatic tumor PDL-1 score (r=0.213; p=0.015). In our study, MHC-1 was found to be higher in primary tumors than metastatic tumors, although not statistically significant (p=0.054). The results of our study showed high MHC-1 and low PDL-1 expression in primary tumors and low MHC-1 and high PDL-1 expression in metastatic tumors. These results reveal different biological characteristics of primary and metastatic tumor cells.

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