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ADAMTS expression in colorectal cancer.

Filou S, Korpetinou A, Kyriakopoulou D, Bounias D, Stavropoulos M, Ravazoula P, Papachristou DJ, Theocharis AD, Vynios DH - PLoS ONE (2015)

Bottom Line: An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated.Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated.Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.

ABSTRACT
ADAMTSs are a family of secreted proteinases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). By acting on a large panel of extracellular substrates, they control several cell functions such as fusion, adhesion, proliferation and migration. Through their thrombospondin motifs they also possess anti-angiogenic properties. We investigated whether ADAMTSs participate in colorectal cancer progression and invasion. Their expression was investigated at both mRNA and protein levels. Using RT-PCR, the expression of ADAMTS-1, -4, -5 and ADAMTS-20 was estimated in colorectal tumors of different cancer stage and anatomic site and 3 cell lines of different aggressiveness. An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated. Western blot analysis further supported the RT-PCR findings, revealing in addition the degradation of ADAMTS-1 and -20 in cancer. In situ expression and localization of ADAMTS-1, -4, -5 and -20 was also investigated by immunohistochemical analysis. Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated. Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM.

No MeSH data available.


Related in: MedlinePlus

Expression of ADAMTSs in healthy and cancerous colon tissues.Semi-quantitative RT-PCR analysis of (A) ADAMTS-1, (C) ADAMTS-4, (E) ADAMTS-5 and (G) ADAMTS-20. Values are the mean GAPDH-normalized ± S.D. Protein distribution of (B) ADAMTS-1, (D) ADAMTS-4, (F) ADAMTS-5 and (H) ADAMTS-20. *P≤0.05; statistically significant differences compared to healthy tissues. **P≤0.05; statistically significant differences compared to stage A. ***P≤0.05; statistically significant differences compared to stage B. Healthy Cecum, Rectum and Sigmoid colon tissues are shown; A-C: Duke’s CRC stages. Arrows indicate the migration of molecular mass markers. PBS, GdnHCl and Triton are the sequential extracting solutions used (see text).
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pone.0121209.g004: Expression of ADAMTSs in healthy and cancerous colon tissues.Semi-quantitative RT-PCR analysis of (A) ADAMTS-1, (C) ADAMTS-4, (E) ADAMTS-5 and (G) ADAMTS-20. Values are the mean GAPDH-normalized ± S.D. Protein distribution of (B) ADAMTS-1, (D) ADAMTS-4, (F) ADAMTS-5 and (H) ADAMTS-20. *P≤0.05; statistically significant differences compared to healthy tissues. **P≤0.05; statistically significant differences compared to stage A. ***P≤0.05; statistically significant differences compared to stage B. Healthy Cecum, Rectum and Sigmoid colon tissues are shown; A-C: Duke’s CRC stages. Arrows indicate the migration of molecular mass markers. PBS, GdnHCl and Triton are the sequential extracting solutions used (see text).

Mentions: RNA levels of ADAMTSs were examined in healthy cecum, sigmoid and rectum. Of all proteases investigated, ADAMTS-1 showed the highest expression (more than double to the internal control-GAPDH), while ADAMTS-5 was the less expressed protease (almost at zero level) (data not shown). RT-PCR analyses indicated that ADAMTS-1 was down-regulated in cancer specimens of any stage compared to the healthy colon, with the greatest decrease to about 20% in stage A specimens (Fig. 4A). These data are in agreement with previous studies, where ADAMTS-1 had been found to be down-regulated in many types of cancer [21, 22]. A different expression pattern from ADAMTS-1 was observed for ADAMTS-4 and-5, which were found to be overexpressed in stage C specimens; almost 14-fold and 20-fold compared to healthy colon tissue, respectively (Fig. 4C, E). These data were in agreement with previous studies in other types of cancer, where ADAMTS-4 and -5 had been found to be over-expressed in order to degrade ECM proteoglycans, such as agreecan and versican to facilitate cancer cell invasion [24, 25]. Following the same experimental procedure for ADAMTS-20, it was found elevated in stage A and B specimens compared to the healthy tissues by 50% and 100%, respectively, but in stage C specimens it exhibited a decrease to 20% (Fig. 4G).


ADAMTS expression in colorectal cancer.

Filou S, Korpetinou A, Kyriakopoulou D, Bounias D, Stavropoulos M, Ravazoula P, Papachristou DJ, Theocharis AD, Vynios DH - PLoS ONE (2015)

Expression of ADAMTSs in healthy and cancerous colon tissues.Semi-quantitative RT-PCR analysis of (A) ADAMTS-1, (C) ADAMTS-4, (E) ADAMTS-5 and (G) ADAMTS-20. Values are the mean GAPDH-normalized ± S.D. Protein distribution of (B) ADAMTS-1, (D) ADAMTS-4, (F) ADAMTS-5 and (H) ADAMTS-20. *P≤0.05; statistically significant differences compared to healthy tissues. **P≤0.05; statistically significant differences compared to stage A. ***P≤0.05; statistically significant differences compared to stage B. Healthy Cecum, Rectum and Sigmoid colon tissues are shown; A-C: Duke’s CRC stages. Arrows indicate the migration of molecular mass markers. PBS, GdnHCl and Triton are the sequential extracting solutions used (see text).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4364768&req=5

pone.0121209.g004: Expression of ADAMTSs in healthy and cancerous colon tissues.Semi-quantitative RT-PCR analysis of (A) ADAMTS-1, (C) ADAMTS-4, (E) ADAMTS-5 and (G) ADAMTS-20. Values are the mean GAPDH-normalized ± S.D. Protein distribution of (B) ADAMTS-1, (D) ADAMTS-4, (F) ADAMTS-5 and (H) ADAMTS-20. *P≤0.05; statistically significant differences compared to healthy tissues. **P≤0.05; statistically significant differences compared to stage A. ***P≤0.05; statistically significant differences compared to stage B. Healthy Cecum, Rectum and Sigmoid colon tissues are shown; A-C: Duke’s CRC stages. Arrows indicate the migration of molecular mass markers. PBS, GdnHCl and Triton are the sequential extracting solutions used (see text).
Mentions: RNA levels of ADAMTSs were examined in healthy cecum, sigmoid and rectum. Of all proteases investigated, ADAMTS-1 showed the highest expression (more than double to the internal control-GAPDH), while ADAMTS-5 was the less expressed protease (almost at zero level) (data not shown). RT-PCR analyses indicated that ADAMTS-1 was down-regulated in cancer specimens of any stage compared to the healthy colon, with the greatest decrease to about 20% in stage A specimens (Fig. 4A). These data are in agreement with previous studies, where ADAMTS-1 had been found to be down-regulated in many types of cancer [21, 22]. A different expression pattern from ADAMTS-1 was observed for ADAMTS-4 and-5, which were found to be overexpressed in stage C specimens; almost 14-fold and 20-fold compared to healthy colon tissue, respectively (Fig. 4C, E). These data were in agreement with previous studies in other types of cancer, where ADAMTS-4 and -5 had been found to be over-expressed in order to degrade ECM proteoglycans, such as agreecan and versican to facilitate cancer cell invasion [24, 25]. Following the same experimental procedure for ADAMTS-20, it was found elevated in stage A and B specimens compared to the healthy tissues by 50% and 100%, respectively, but in stage C specimens it exhibited a decrease to 20% (Fig. 4G).

Bottom Line: An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated.Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated.Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.

ABSTRACT
ADAMTSs are a family of secreted proteinases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). By acting on a large panel of extracellular substrates, they control several cell functions such as fusion, adhesion, proliferation and migration. Through their thrombospondin motifs they also possess anti-angiogenic properties. We investigated whether ADAMTSs participate in colorectal cancer progression and invasion. Their expression was investigated at both mRNA and protein levels. Using RT-PCR, the expression of ADAMTS-1, -4, -5 and ADAMTS-20 was estimated in colorectal tumors of different cancer stage and anatomic site and 3 cell lines of different aggressiveness. An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated. Western blot analysis further supported the RT-PCR findings, revealing in addition the degradation of ADAMTS-1 and -20 in cancer. In situ expression and localization of ADAMTS-1, -4, -5 and -20 was also investigated by immunohistochemical analysis. Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated. Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM.

No MeSH data available.


Related in: MedlinePlus