Serum samples from pancreatectomized patients contain trypsinogen immunoreactivity

doi:10.1016/S0022-2143(96)90118-3

Journal of Laboratory and Clinical Medicine

Volume 128, Issue 1, July 1996, Pages 98-102

https://doi.org/10.1016/S0022-2143(96)90118-3 Get rights and content

Abstract

The concentrations of trypsinogen-1 and -2 in serum samples from patients who have undergone pancreatectomy were measured by highly sensitive and specific time-resolved immunofluorometric assays. The isoenzyme pattern was determined by ion-exchange chromatography and determination of immunoreactivity in the fractions. All samples contained trypsinogen-2, the mean level being one fifth of that in healthy controls. Trypsinogen-1 was detected in one of nine samples. In addition to the main trypsinogen isoenzymes, we observed in normal serum two trypsinogen isoenzymes previously found in mucinous ovarian cyst fluid. Our results suggest that trypsinogen is not exclusively expressed by the pancreas and certain tumors but that it also may be produced by normal extrapancreatic tissues. This should be considered when an assay of trypsinogen in serum is used for clinical purposes.

References (23)

G Scheele et al.
Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sufate gel electrophoresis
Gastroenterology
(1981)
H Rinderknecht et al.
Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid
Gastroenterology
(1984)
C Largman et al.
Demonstration of human pancreatic anionic trypsinogen in normal serum by radioimmunoassay
Biochim Biophys Acta
(1978)
E Elias et al.
Diagnostic importance of changes in circulating concentrations of immunoreactive trypsin
Lancet
(1977)
E Koivunen et al.
Human ovarian tumor-associated trypsin
H Halila et al.
Pancreatic secretory trypsin inhibitor in patients who have undergone pancreatectomy
Clin Chim Acta
(1985)
U Wiegand et al.
Cloning of the cDNA encoding human brain trypsinogen and characterization of its product
Gene
(1993)
PA Mallory et al.
Human pancreatic enzymes: characterization of anionic human trypsin
Biochemistry
(1973)
A Borgström et al.
Radioimmunological determination and characterization of cathodal trypsin-like immunoreactivity in normal human plasma
Scand J Clin Lab Invest
(1976)
MC Geokas et al.
Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay
Am J Physiol
(1979)

J Florholmen et al.

Radioimmunoassay of cationic trypsin-like immunoreactivity in man

Scand J Gastroenterol

(1984)

Cited by (10)

Intracellular co-localization of trypsin-2 and matrix metalloprotease-9: Possible proteolytic cascade of trypsin-2, MMP-9 and enterokinase in carcinoma
2008, Experimental Cell Research
Tumor-associated trypsin-2 and matrix metalloprotease-9 (MMP-9) are associated with cancer, particularly with invasive squamous cell carcinomas. They require activation for catalytical competence via proteolytic cascades. One cascade is formed by enterokinase, trypsin-2 and MMP-9; enterokinase activates trypsinogen-2 to trypsin-2, which is an efficient proMMP-9 activator. We describe here that oral squamous cell carcinomas express all members of this cascade: MMP-9, trypsin-2 and enterokinase. The expression of enterokinase in a carcinoma cell line not derived from the duodenum was shown here for the first time. Enterokinase directly cleaved proMMP-9 at the Lys⁶⁵-Ser⁶⁶ site, but failed to activate it in vitro. We demonstrated by confocal microscopy that MMP-9 and trypsin-2 co-localized in intracellular vesicles of the carcinoma cells. This co-localization of trypsin-2 and MMP-9 resulted in intracellular proMMP-9 processing that represented fully or partially activated MMP-9. However, although both proteases were present also in various bone tumor tissues, MMP-9 and trypsin-2 never co-localized at the cellular level in these tissues. This suggests that the intracellular vesicular co-localization, storage and possible activation of these proteases may be a unique feature for aggressive epithelial tumors, such as squamous cell carcinomas, but not for tumors of mesenchymal origin.
Trypsins and their role in carcinoma growth
2006, Experimental Cell Research
Citation Excerpt :
TAT-2 and trypsin-2 derived from pancreas have identical aminoterminal sequence, molecular weight, and immunoreactivity, but they differ in their activity against synthetic substrates, enzyme stability, and isoelectric point. These differences are probably due to post-translational modification that is different in pancreas and carcinomas [43,44,50,58]. The nucleotide sequence of TAT-2 and pancreatic trypsin-2 was identical except for one base substitution (G to A) [44].
There are more than 100 distinct types of cancer, and subtypes can be found within specific organs. Cancer progression is a complex multi-step process. These steps reflect alterations that drive the progressive transformation of normal cells into highly malignant ones. One critical step in tumor growth and invasion is the proteolytic processing of the extracellular matrix environment. The degradation of the extracellular matrix not only enables cell migration, invasion, and metastasis formation, but also affects cell behavior in multiple ways; on one hand by cleaving extracellular matrix bound growth factors and on the other hand by inhibiting angiogenesis into the tumor by liberating cryptic endogenous inhibitors of angiogenesis. Serine proteases and matrix metalloproteases are families of proteolytic enzymes involved in physiological and pathological extracellular matrix and basement membrane processing. In this review, we will focus on the role and activation of trypsinogens, a family of serine proteases, in cancer progression.
Activation of type IV procollagenases by human tumor-associated trypsin- 2
1997, Journal of Biological Chemistry
Increased production of proteinases, such as matrix metalloproteinases (MMPs), is a characteristic feature of malignant tumors. Some human cancers and cell lines derived from them also express trypsinogen, but the function of the extrapancreatic trypsin has remained unclear. In this study we cloned and sequenced trypsinogen-2 cDNA from human COLO 205 colon carcinoma cells and characterized the ability of the enzyme to activate latent human type IV procollagenases (proMMP-2 and proMMP-9). As shown by cloning and N-terminal amino acid sequencing, the amino acid sequence of tumor-associated trypsin-2 is identical to that of pancreatic trypsin-2. We found that both pancreatic trypsin-2 and tumor cell-derived trypsin-2 are efficient activators of proMMP-9 and are capable of activating proMMP-9 at a molar ratio of 1:1000, the lowest reported so far. Human trypsin-2 was a more efficient activator than widely used bovine trypsin and converted the 92-kDa proMMP-9 to a single 77-kDa product that was not fragmented further. The single peptide bond cleaved by trypsin-2 in proMMP-9 was Arg⁸⁷-Phe⁸⁸. The generation of the 77-kDa species coincided with the increase in specific activity of MMP-9. In contrast, trypsin-2 only partially activated proMMP-2. Trypsin-2 cleaved the Arg⁹⁹-Lys¹⁰⁰ peptide bond of proMMP-2 generating 62–65-kDa MMP-2 species. Trypsin-2-induced proMMP-2 and -9 conversions were inhibited by tumor-associated trypsin inhibitor added either prior to or during activation indicating that proMMPs were not activated autocatalytically. Trypsin-2 also activated proMMPs associated with tissue inhibitor of matrix metalloproteinases, the complexes of which are thought to be the major MMP forms in vivo. The ability of human tumor cell-derived trypsin-2 to activate latent MMPs suggests a role for trypsin-2 in initiating the proteinase cascade that mediates tumor invasion and metastasis formation.
Endogenous proteases in tumoral progression
2017, Pathophysiological Aspects of Proteases
Biomarker development, from bench to bedside
2016, Critical Reviews in Clinical Laboratory Sciences
Human trypsinogens in the pancreas and in cancer
2010, Scandinavian Journal of Clinical and Laboratory Investigation

View all citing articles on Scopus

^☆: Supported by grants from The Academy of Finland, the Sigrid Jusélius Foundation, The Finnish Cancer Institute, and The Finnish Social Insurance Institution.

View full text

Original articleSerum samples from pancreatectomized patients contain trypsinogen immunoreactivity☆

Abstract

Gastroenterology

Gastroenterology

Biochim Biophys Acta

Lancet

Clin Chim Acta

Gene

Human pancreatic enzymes: characterization of anionic human trypsin

Biochemistry

Radioimmunological determination and characterization of cathodal trypsin-like immunoreactivity in normal human plasma

Scand J Clin Lab Invest

Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay

Am J Physiol

Radioimmunoassay of cationic trypsin-like immunoreactivity in man

Scand J Gastroenterol

Original article
Serum samples from pancreatectomized patients contain trypsinogen immunoreactivity☆