The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies

Tse, Ryan Tsz‐Hei; Wong, Christine Yim‐Ping; Chiu, Peter Ka‐Fung; Ng, Chi‐Fai

doi:10.3390/ijms23031258

Cited by 23 publications

(17 citation statements)

References 47 publications

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“…The significant increase of polyamines established at the site of cancer compared to non-neoplastic mucosa and adjacent colonic mucosa, suggests that polyamines can serve as oncological markers in early detection of colon cancer [33]. The increase of the main polyamines in our investigation, especially spermine, correlates with the findings of this and other authors [33,34]. It has been known that the mechanism by which cancer cells enhance their metastatic potential is their response to hypoxia.…”

Section: Discussionsupporting

confidence: 87%

Altered arginine metabolism in colon cancer: A sign of increased proliferative potential of tumor-adjacent tissue

Branković

Stanojević

Veljković

et al. 2022

ARCH BIOL SCI BELGRA

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Colorectal cancer (CRC) is one of the most frequent forms of malignant tumors in the human population. The literature data about the role of arginine metabolism in CRC point out its double-faced role. In three tissue specimens of 50 patients who underwent surgical resection for colon adenocarcinoma (tumor, adjacent and healthy tissues more than 10 cm from the tumor border - at the incision margin) taken during surgery, polyamines and the concentration of NO2+NO3 and arginase activity were determined. Polyamine levels and arginase activity were significantly increased in cancer and adjacent tissue specimens compared to healthy ones, while the level of NO2+NO3 was significantly lower in cancer compared to both adjacent and healthy tissues. The high polyamine content in the adjacent colonic mucosa indicates a high proliferative potential of tumor-adjacent tissue. Although we found individual correlations indicating the possible prognostic value of arginase, the performed statistical analysis did not show a predictive significance of arginase activity in the examined tissue specimens for five-year survival of the patients. Nevertheless, the obtained results provide the rationale for further studies of arginine metabolism in tissue specimens after surgery in patients with CRC, which could be useful in the evaluation of the risk for tumor growth, recurrence, metastases and survival after surgical intervention.

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Section: Discussionsupporting

confidence: 87%

Altered arginine metabolism in colon cancer: A sign of increased proliferative potential of tumor-adjacent tissue

Branković

Stanojević

Veljković

et al. 2022

ARCH BIOL SCI BELGRA

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“…However, this feature is disadvantageous as salivary polyamines cannot be used to detect DCIS. Polyamine levels were consistently elevated in both pancreatic tissues and urine samples Conventionally, only N 1 , N 12 -diacetylspermine was evaluated as a biomarker; however, a combination of various acetylated forms of urinary polyamines showed potential in screening various cancers [ 91 ]. Similar data have been reported in colon cancer cohorts [ 92 , 93 ].…”

Section: Discussionmentioning

confidence: 99%

Salivary Metabolomics for Oral Cancer Detection: A Narrative Review

Panneerselvam¹,

Ishikawa

Krishnan

et al. 2022

Metabolites

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The development of low- or non-invasive screening tests for cancer is crucial for early detection. Saliva is an ideal biofluid containing informative components for monitoring oral and systemic diseases. Metabolomics has frequently been used to identify and quantify numerous metabolites in saliva samples, serving as novel biomarkers associated with various conditions, including cancers. This review summarizes the recent applications of salivary metabolomics in biomarker discovery in oral cancers. We discussed the prevalence, epidemiologic characteristics, and risk factors of oral cancers, as well as the currently available screening programs, in India and Japan. These data imply that the development of biomarkers by itself is inadequate in cancer detection. The use of current diagnostic methods and new technologies is necessary for efficient salivary metabolomics analysis. We also discuss the gap between biomarker discovery and nationwide screening for the early detection of oral cancer and its prevention.

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“…To the best of our knowledge, we first provided the evidence that spermine can promote the expression of PD-L1 in HCC. Considering that elevated level of spermine in tumor tissues has been observed in patients with breast cancer, lung cancer or pancreatic cancer [ 60 ], we suppose that spermine can also promote tumor cell immune escape through inducing PD-L1 expression in these cancers. However, our study did not investigate whether spermine could induce the expression of PD-L1 in normal tissues, which is a limitation of this study.…”

Section: Discussionmentioning

confidence: 99%

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma

et al. 2022

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Background Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism. Methods Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, β-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells. Results Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent β-catenin stabilization and nuclear translocation. Nuclear β-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells. Conclusions This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma.

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The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies

Cited by 23 publications

References 47 publications

Altered arginine metabolism in colon cancer: A sign of increased proliferative potential of tumor-adjacent tissue

Altered arginine metabolism in colon cancer: A sign of increased proliferative potential of tumor-adjacent tissue

Salivary Metabolomics for Oral Cancer Detection: A Narrative Review

Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma

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