Synergistic interaction between galectin-3 and carcinoembryonic antigen promotes colorectal cancer metastasis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

In this study, we investigated the role of galectin-3 and carcinoembryonic antigen (CEA) in metastasis and survival of colorectal cancer (CRC) patients. CEA interacted with galectin-3 at the cell surface and cytoplasm of Caco2 and DLD1 CRC cells. Knocking down galectin-3 did not affect CEA expression in CRC cells. However, there was a dose-dependent increase in CRC cell migration upon addition of small amounts of exogenous CEA (≤1ng/ml). Galectin-3 knockdown blocked induction of CRC cell migration by CEA, suggesting interaction between galectin-3 and CEA was necessary for CRC cell migration. Exogenous CEA and galectin-3 synergistically promoted migration of galectin-3 knockdown DLD1 cells. Immunohistochemical analysis showed that CEA co-localized with galectin-3 in CRC patient tissues. In additon, advanced stage CRC patients had higher serum galectin-3 and CEA levels than early stage CRC patients. High serum CEA and galectin-3 levels correlated with advanced N stage and poor survival in CRC patients. These findings suggest interaction between galectin-3 and CEA promotes CRC migration and metastasis, and correlates with poor survival of CRC patients. Thus combinatorial therapy targeting galectin-3 and CEA may improve outcomes for advanced stage CRC patients.

Related collections

Most cited references 27

Record: found
Abstract: found
Article: not found

Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium.

Vladislav Glinsky, Gennadi Glinsky, Olga Glinskii … (2003)

The two major theories of cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, view tumor cell adhesion to blood vessel endothelia and cancer cell aggregation as corresponding key components of the metastatic process. Here, we demonstrate in vitro, ex vivo, and in vivo that metastatic breast and prostate carcinoma cells form multicellular homotypic aggregates at the sites of their primary attachment to the endothelium. Our results suggest that metastatic cell heterotypic adhesion to the microvascular endothelium and homotypic aggregation represent two coordinated subsequent steps of the metastatic cascade mediated largely by similar molecular mechanisms, specifically by interactions of tumor-associated Thomsen-Friedenreich glycoantigen with the beta-galactoside-binding protein, galectin-3. In addition to inhibiting neoplastic cell adhesion to the endothelium and homotypic aggregation, disrupting this line of intercellular communication using synthetic Thomsen-Friedenreich antigen masking and Thomsen-Friedenreich antigen mimicking compounds greatly affects cancer cell clonogenic survival and growth as well. Thus, beta-galactoside-mediated intravascular heterotypic and homotypic tumor cell adhesive interactions at the sites of a primary attachment to the microvascular endothelium could play an important role during early stages of hematogenous cancer metastasis.

0 comments Cited 70 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Extending the frontiers of surgical therapy for hepatic colorectal metastases: is there a limit?

V Khatri, Jacques Belghiti, Nicholas J. Petrelli (2005)

Hepatic resection for colorectal metastases, limited to the liver, has become the standard of care, and currently remains the only potentially curative therapy. Numerous single institutional reports have demonstrated long-term survival, and there are no other treatment options that have shown a survival plateau. However, curative resection is possible in less than 25% of patients with disease limited to the liver, which consequently translates into only 5% to 10% of the original group developing colorectal cancer. To increase the number of patients who could benefit from hepatic resection, the last decade has seen considerable effort directed towards the following areas, (1) refining prognostic factors that would improve patient selection, (2) advancements in surgical technique such as, use of intraoperative ultrasonography, controlling hemorrhage through use of vascular clamping techniques supplemented with low central venous pressure anesthesia, availability of novel devices for parenchymal transection, and controlled anatomic hepatectomy with Glissonian technique, and (3) novel approaches to permit curative hepatic resection such as, preoperative portal vein embolization for hypertrophy of future liver remnant and staged hepatic resection. This article reviews development of these innovative multidisciplinary modalities and the aggressive surgical approach that has been adopted to extend the frontiers of surgical therapy for colorectal hepatic metastases.

0 comments Cited 50 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Overexpressed Galectin-3 in Pancreatic Cancer Induces Cell Proliferation and Invasion by Binding Ras and Activating Ras Signaling

SHUMEI SONG, Baoan Ji, Vijaya Ramachandran … (2012)

Pancreatic cancer (PDAC) is a lethal disease with a five-year survival of 3–5%. Mutations in K-Ras are found in nearly all cases, but K-Ras mutations alone are not sufficient for the development of PDAC. Additional factors contribute to activation of Ras signaling and lead to tumor formation. Galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in PDAC. We therefore investigated the functional role of Gal-3 in pancreatic cancer progression and its relationship to Ras signaling. Expression of Gal-3 was determined by immunohistochemistry, Q-PCR and immunoblot. Functional studies were performed using pancreatic cell lines genetically engineered to express high or low levels of Gal-3. Ras activity was examined by Raf pull-down assays. Co-immunoprecipitation and immunofluorescence were used to assess protein-protein interactions. In this study, we demonstrate that Gal-3 was highly up-regulated in human tumors and in a mutant K-Ras mouse model of PDAC. Down-regulation of Gal-3 by lentivirus shRNA decreased PDAC cell proliferation and invasion in vitro and reduced tumor volume and size in an orthotopic mouse model. Gal-3 bound Ras and maintained Ras activity; down-regulation of Gal-3 decreased Ras activity as well as Ras down-stream signaling including phosphorylation of ERK and AKT and Ral A activity. Transfection of Gal-3 cDNA into PDAC cells with low-level Gal-3 augmented Ras activity and its down-stream signaling. These results suggest that Gal-3 contributes to pancreatic cancer progression, in part, by binding Ras and activating Ras signaling. Gal-3 may therefore be a potential novel target for this deadly disease.

0 comments Cited 48 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 22 September 2017

Publication date (Electronic): 27 June 2017

Volume: 8

Issue: 37

Pages: 61935-61943

Affiliations

¹ Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

² Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan

³ Chang Gung University, College of Medicine, Kaohsiung, Taiwan

⁴ Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

⁵ School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan

⁶ Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Author notes

Correspondence to: Chang-Chun Hsiao, cchsiao@ 123456mail.cgu.edu.tw

Article

Publisher ID: 18721

DOI: 10.18632/oncotarget.18721

PMC ID: 5617476

PubMed ID: 28977916

SO-VID: 6b9abc1e-88ca-4fd9-9e17-944244313439

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Synergistic interaction between galectin-3 and carcinoembryonic antigen promotes colorectal cancer metastasis

Read this article at

Abstract

Related collections

Karger: Oncology

Most cited references 27

Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium.

Extending the frontiers of surgical therapy for hepatic colorectal metastases: is there a limit?

Overexpressed Galectin-3 in Pancreatic Cancer Induces Cell Proliferation and Invasion by Binding Ras and Activating Ras Signaling

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 259

Cited by 9

Most referenced authors 354