Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2010

01-08-2010 | Colorectal Cancer

Stromal CXCR4 and CXCL12 Expression is Associated with Distant Recurrence and Poor Prognosis in Rectal Cancer After Chemoradiotherapy

Published in: Annals of Surgical Oncology | Issue 8/2010

Login to get access

Abstract

Background

Distant recurrence remains the major cause of mortality in rectal cancer patients with preoperative chemoradiotherapy (CRT). Recently, cancer stroma has been implicated in influencing proliferation, invasion, and metastasis of cancer cells. It has been reported that expression of CXCR4 and its ligand CXCL12 are associated with migration, invasion, and proliferation of colorectal cancer.

Materials and Methods

A total of 53 patients with rectal cancer underwent preoperative CRT. Total RNAs of residual rectal cancer stromal cells after CRT were obtained from formalin-fixed paraffin-embedded (FFPE) specimens using microdissection. The expression levels of CXCR4 and CXCL12 genes were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical staining of these markers after CRT was also investigated.

Results

Of the 53 patients, 16 (30.1%) and 14 (26.4%) showed detectable CXCR4 and CXCL12 levels, respectively. We found a significant positive correlation between expression levels of CXCR4 and CXCL12. Patients who developed distant recurrence had twofold higher expression levels of both CXCR4 and CXCL12 compared with those without recurrence after CRT (P < 0.01). Elevated expression levels were also associated with poor probability of recurrence-free survival in both genes (P < 0.01). Additionally, positive CXCL12 expression, but not CXCR4, was significantly correlated with poorer overall survival (P < 0.01). CXCR4 and CXCL12 expression determined using immunohistochemistry was observed in not only cancer but also stromal cells.

Conclusion

Our results suggest that evaluation of the expression of both genes may be useful for predicting distant recurrence and poor prognosis in rectal cancer patients treated with preoperative CRT followed by surgery.
Literature
1.
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefPubMed
2.
Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005;241:829–36 (discussion 836–8).CrossRefPubMed
3.
Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.CrossRefPubMed
4.
Kucia M, Jankowski K, Reca R, et al. CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol. 2004;35:233–45.CrossRefPubMed
5.
Salvucci O, Yao L, Villalba S, et al. Regulation of endothelial cell branching morphogenesis by endogenous chemokine stromal-derived factor-1. Blood. 2002;99:2703–11.CrossRefPubMed
6.
Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–6.CrossRefPubMed
7.
Yoshitake N, Fukui H, Yamagishi H, et al. Expression of SDF-1 alpha and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer. Br J Cancer. 2008;98:1682–9.CrossRefPubMed
8.
Bajetto A, Barbieri F, Pattarozzi A, et al. CXCR4 and SDF1 expression in human meningiomas: a proliferative role in tumoral meningothelial cells in vitro. Neuro Oncol. 2007;9:3–11.CrossRefPubMed
9.
Dewan MZ, Ahmed S, Iwasaki Y, et al. Stromal cell-derived factor-1 and CXCR4 receptor interaction in tumor growth and metastasis of breast cancer. Biomed Pharmacother. 2006;60:273–6.CrossRefPubMed
10.
Vianello F, Papeta N, Chen T, et al. Murine B16 melanomas expressing high levels of the chemokine stromal-derived factor-1/CXCL12 induce tumor-specific T cell chemorepulsion and escape from immune control. J Immunol. 2006;176:2902–14.PubMed
11.
Schimanski CC, Galle PR, Moehler M. Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors. World J Gastroenterol. 2008;14:4721–4.CrossRefPubMed
12.
Koizumi K, Hojo S, Akashi T, et al. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response. Cancer Sci. 2007;98:1652–8.CrossRefPubMed
13.
14.
Kim J, Takeuchi H, Lam ST, et al. Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005;23:2744–53.CrossRefPubMed
15.
Matsusue R, Kubo H, Hisamori S, et al. Hepatic stellate cells promote liver metastasis of colon cancer cells by the action of SDF-1/CXCR4 axis. Ann Surg Oncol. 2009;16:2645–53.CrossRefPubMed
16.
Ottaiano A, Franco R, Aiello Talamanca A, et al. Overexpression of both CXC chemokine receptor 4 and vascular endothelial growth factor proteins predicts early distant relapse in stage II-III colorectal cancer patients. Clin Cancer Res. 2006;12:2795–803.CrossRefPubMed
17.
Sund M, Kalluri R. Tumor stroma derived biomarkers in cancer. Cancer Metastasis Rev. 2009;28:177–83.CrossRefPubMed
18.
19.
Tse JC, Kalluri R. Mechanisms of metastasis: epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem. 2007;101:816–29.CrossRefPubMed
20.
Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature. 2004;432:332–7.CrossRefPubMed
21.
Finak G, Bertos N, Pepin F, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14:518–27.CrossRefPubMed
22.
Kusunoki M, Yanagi H, Noda M, Yamamura T. The usefulness of pharmacokinetic modulating chemotherapy (UFT plus 5FU) in the treatment of unresectable colorectal carcinomas. Oncol Rep. 1999;6:547–52.PubMed
23.
Yoshikawa R, Kusunoki M, Yanagi H, et al. Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating chemotherapy. Cancer Res. 2001;61:1029–37.PubMed
24.
Sugihara K, Japanese Society for Cancer of the Colon and Rectum. General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum, and Anus. Tokyo: Kanehara & Co; 2006.
25.
Bijwaard KE, Aguilera NS, Monczak Y, et al. Quantitative real-time reverse transcription-PCR assay for cyclin D1 expression: utility in the diagnosis of mantle cell lymphoma. Clin Chem. 2001;47:195–201.PubMed
26.
Brand S, Dambacher J, Beigel F, et al. CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation. Exp Cell Res. 2005;310:117–30.CrossRefPubMed
27.
Beider K, Abraham M, Begin M, et al. Interaction between CXCR4 and CCL20 pathways regulates tumor growth. PLoS One. 2009;4:e5125.CrossRefPubMed
28.
Potenta S, Zeisberg E, Kalluri R. The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer. 2008;99:1375–9.CrossRefPubMed
29.
Zeisberg EM, Potenta S, Xie L, et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res. 2007;67:10123–8.CrossRefPubMed
30.
Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.CrossRefPubMed
31.
Onoue T, Uchida D, Begum NM, et al. Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells. Int J Oncol. 2006;29:1133–8.PubMed
32.
Taki M, Higashikawa K, Yoneda S, et al. Up-regulation of stromal cell-derived factor-1alpha and its receptor CXCR4 expression accompanied with epithelial-mesenchymal transition in human oral squamous cell carcinoma. Oncol Rep. 2008;19:993–8.PubMed
Metadata
Title
Stromal CXCR4 and CXCL12 Expression is Associated with Distant Recurrence and Poor Prognosis in Rectal Cancer After Chemoradiotherapy
Publication date
01-08-2010
Published in
Annals of Surgical Oncology / Issue 8/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-0970-y

Other articles of this Issue 8/2010

Annals of Surgical Oncology 8/2010 Go to the issue

Head and Neck Oncology

Improvements in the Staging of Cutaneous Squamous-Cell Carcinoma in the 7th Edition of the AJCC Cancer Staging Manual

Breast Oncology

Incidental Breast Lesions Identified by 18F-Fluorodeoxyglucose-Positron Emission Tomography

Translational Research and Biomarkers

Epigenetic Inactivation of the Thyroid Hormone Receptor β1 Gene at 3p24.2 in Lung Cancer

Gastrointestinal Oncology

Improved Long-Term Quality of Life in Patients with Laparoscopy-Assisted Distal Gastrectomy with Jejunal Pouch Interposition for Early Gastric Cancer

Gastrointestinal Oncology

Histological Regression of Squamous Esophageal Carcinoma Assessed by Percentage of Residual Viable Cells after Neoadjuvant Chemoradiation is an Important Prognostic Factor

Melanomas

Predicting Survival Outcome of Localized Melanoma: An Electronic Prediction Tool Based on the AJCC Melanoma Database