Significance of Alkaline Phosphatase Isozymes in the Monitoring of Patients with Colorectal Carcinoma

Harmenberg, Ulrika; Frödin, Jan Erik; Ljungdahl-Ståhle, E.; Mellstedt, Håkan; Wahrén, Britta; Stigbrand, Torgny

doi:10.1159/000217619

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…ALPPs are elevated in some cancers, including colorectal cancer (36), and have been correlated with folate levels. SPR is involved in the folate cycle as well as in cell proliferation (37).…”

Section: Discussionmentioning

confidence: 99%

Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells

Sahlberg

Mortensen

Haglöf

et al. 2016

International Journal of Oncology

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AKT is a central protein in many cellular pathways such as cell survival, proliferation, glucose uptake, metabolism, angiogenesis, as well as radiation and drug response. The three isoforms of AKT (AKT1, AKT2 and AKT3) are proposed to have different physiological functions, properties and expression patterns in a cell type-dependent manner. As of yet, not much is known about the influence of the different AKT isoforms in the genome and their effects in the metabolism of colorectal cancer cells. In the present study, DLD-1 isogenic AKT1, AKT2 and AKT1/2 knockout colon cancer cell lines were used as a model system in conjunction with the parental cell line in order to further elucidate the differences between the AKT isoforms and how they are involved in various cellular pathways. This was done using genome wide expression analyses, metabolic profiling and cell migration assays. In conclusion, downregulation of genes in the cell adhesion, extracellular matrix and Notch-pathways and upregulation of apoptosis and metastasis inhibitory genes in the p53-pathway, confirm that the knockout of both AKT1 and AKT2 will attenuate metastasis and tumor cell growth. This was verified with a reduction in migration rate in the AKT1 KO and AKT2 KO and most explicitly in the AKT1/2 KO. Furthermore, the knockout of AKT1, AKT2 or both, resulted in a reduction in lactate and alanine, suggesting that the metabolism of carbohydrates and glutathione was impaired. This was further verified in gene expression analyses, showing downregulation of genes involved in glucose metabolism. Additionally, both AKT1 KO and AKT2 KO demonstrated an impaired fatty acid metabolism. However, genes were upregulated in the Wnt and cell proliferation pathways, which could oppose this effect. AKT inhibition should therefore be combined with other effectors to attain the best effect.

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Section: Discussionmentioning

confidence: 99%

Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells

Sahlberg

Mortensen

Haglöf

et al. 2016

International Journal of Oncology

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“…In our study, the first area had the same hydrophilicity as the heat-sensitive LAP fraction according to the earlier studies by Koshida et al [25], but it also contained PLAP. The PLAP-like sub stance found in area I may correlate with the heat-sensitive PLAP-like enzyme as de scribed earlier in sera from patients with advanced colorectal cancer [22]. A recent publication [34] reported on the cloning of a PLAP-like enzyme from a colorectal cancer cell line.…”

Section: Discussionmentioning

confidence: 61%

“…In a recent work, elevated serum levels of PLAP were seen in patients with advanced colorectal cancer [22], All of the 8 patients investigated had substantially elevated levels of PLAP. The PLAP levels in these sera were analyzed both with a catalytic assay measur ing only heat-stable PLAP enzyme and an immunocatalytic assay measuring both heatstable and heat-sensitive enzyme.…”

Section: Introductionmentioning

confidence: 77%

“…Since PLAP or PLAP-like isozymes are not released into the circulation in signif icant amounts from other tumors, these en zymes have not been regarded as useful tu mor markers for other tumors, even though they have been identified in other tumor tis sues. In a recent work, high amounts of PLAP or PLAP-like isozymes were found in sera from patients with advanced colorectal cancer [22]. This initiated the study of whether the expression of these isozymes is a more general phenomenon related to malig nant transformation.…”

Section: Discussionmentioning

confidence: 99%

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Identification and Characterization of Alkaline Phosphatase Isozymes in Human Colorectal Adenocarcinomas

Harmenberg

Koha²,

Makiya³

et al. 1991

Tumor Biol

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Using alkaline phosphatase isozyme-specific immunocatalytical assays, the content of isozymes was determined in normal mucosas and adenocarcinomas from human colon or rectum. Tumor levels of both the tissue (liver)-unspecific and the placental-like alkaline phosphatase (PLAP-like) were elevated compared to normal mucosas of the same patients. Such elevations have been reported previously, particularly in seminomas and ovarian tumors. In several tumors, moreover, the intestinal isozyme was expressed in lesser amounts than in the adjacent mucosa. The present results indicate that the activation of two of the phosphatase isozymes, including expression of the typical germ cell line phosphatase (the PLAP-like isozyme), may occur even in nongonadal tumors. This may reflect an induction pattern of phosphatase isozymes, with implications for malignant transformation also in other tumors.

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Alkaline Phosphatases as Tumor Markers

Stigbrand¹,

Wahrén²

1992

Serological Cancer Markers

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Significance of Alkaline Phosphatase Isozymes in the Monitoring of Patients with Colorectal Carcinoma

Cited by 8 publications

References 10 publications

Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells

Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells

Identification and Characterization of Alkaline Phosphatase Isozymes in Human Colorectal Adenocarcinomas

Alkaline Phosphatases as Tumor Markers

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