Tumor-associated fibroblasts isolated from colorectal cancer  tissues exhibit increased ICAM-1 expression and affinity for monocytes

Schellerer,Vera   S.; Langheinrich,Melanie; Hohenberger,Werner; Croner,Roland  S.; Merkel,Susanne; Rau,Tilman  T.; Stürzl,Michael; Naschberger,Elisabeth

doi:10.3892/or.2013.2860

Tumor-associated fibroblasts isolated from colorectal cancer tissues exhibit increased ICAM-1 expression and affinity for monocytes

Authors:
- Vera S. Schellerer
- Melanie Langheinrich
- Werner Hohenberger
- Roland S. Croner
- Susanne Merkel
- Tilman T. Rau
- Michael Stürzl
- Elisabeth Naschberger
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Affiliations: Department of Surgery, University Medical Center Erlangen, D-91054 Erlangen, Germany, Department of Pathology, University Medical Center Erlangen, D-91054 Erlangen, Germany, Department of Molecular and Experimental Surgery, University Medical Center Erlangen, D-91054 Erlangen, Germany
Published online on: November 20, 2013 https://doi.org/10.3892/or.2013.2860
Pages: 255-261

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Abstract

Progression of colorectal cancer (CRC) is strongly associated with inflammation and other desmoplastic reactions in the tumor cell-surrounding tissue. We successfully isolated fibroblasts from the desmoplastic stroma of human CRC specimens and uninvolved colon tissue of patients treated surgically for CRC and investigated potential functional capacities. All of the isolated fibroblasts were vimentin‑positive and CK-20/CD45-negative confirming the fibroblast phenotype. Differential expression patterns were detected between tumor‑associated fibroblasts (TAFs) and normal tissue-associated fibroblasts (NAFs) regarding intercellular adhesion molecule-1 (ICAM-1) expression. In 11 of 12 TAF cultures, basal ICAM-1 expression was increased as compared to corresponding NAF cultures (p=0.001). After stimulation of the cultures with interleukin-1β, 8 of the 12 TAF cultures presented higher ICAM-1 levels when compared with the level in the corresponding NAF cultures (p=0.001). Moreover, the adhesive capacity of these cultures for U937 was increased in 8 out of 10 unstimulated and in 10 out of 10 stimulated cultures when TAFs and NAFs were compared. In corresponding tumor tissue sections from the same patients, the amount of ICAM-1-positive fibroblasts was significantly higher than that in the corresponding normal colon mucosa, indicating a tumor-specific effect that was maintained in the isolated cultures. These results indicate that fibroblasts from CRC tissue exhibit an increased affinity for monocytic cells. This increased intercellular interaction may contribute to elongated residence times of monocytes in CRC tissue. Therefore, these isolated fibroblasts are a useful tool for further functional investigation of desmoplastic tissue reactions in CRC.

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1	Saunders M and Iveson T: Management of advanced colorectal cancer: state of the art. Br J Cancer. 95:131–138. 2006. View Article : Google Scholar : PubMed/NCBI
2	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
3	Din FV, Theodoratou E, Farrington SM, Tenesa A, Barnetson RA, Cetnarskyj R, et al: Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut. 59:1670–1679. 2010. View Article : Google Scholar : PubMed/NCBI
4	Wang D and Dubois RN: The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene. 29:781–788. 2010. View Article : Google Scholar : PubMed/NCBI
5	Lakatos PL and Lakatos L: Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol. 14:3937–3947. 2008. View Article : Google Scholar : PubMed/NCBI
6	Strell C, Rundqvist H and Ostman A: Fibroblasts - a key host cell type in tumor initiation, progression, and metastasis. Ups J Med Sci. 117:187–195. 2012. View Article : Google Scholar : PubMed/NCBI
7	Benson V, McMahon AC and Lowe HC: ICAM-1 in acute myocardial infarction: a potential therapeutic target. Curr Mol Med. 7:219–227. 2007. View Article : Google Scholar : PubMed/NCBI
8	Niessen HW, Lagrand WK, Visser CA, Meijer CJ and Hack CE: Upregulation of ICAM-1 on cardiomyocytes in jeopardized human myocardium during infarction. Cardiovasc Res. 41:603–610. 1999. View Article : Google Scholar : PubMed/NCBI
9	Huang WC, Chan ST, Yang TL, Tzeng CC and Chen CC: Inhibition of ICAM-1 gene expression, monocyte adhesion and cancer cell invasion by targeting IKK complex: molecular and functional study of novel α-methylene-γ-butyrolactone derivatives. Carcinogenesis. 25:1925–1934. 2004.PubMed/NCBI
10	van de Stolpe A and van der Saag PT: Intercellular adhesion molecule-1. J Mol Med. 74:13–33. 1996.
11	Ksiazek K, Mikula-Pietrasik J, Catar R, Dworacki G, Winckiewicz M, Frydrychowicz M, et al: Oxidative stress-dependent increase in ICAM-1 expression promotes adhesion of colorectal and pancreatic cancers to the senescent peritoneal mesothelium. Int J Cancer. 127:293–303. 2010.
12	Arteta B, Lasuen N, Lopategi A, Sveinbjörnsson B, Smedsrød B and Vidal-Vanaclocha F: Colon carcinoma cell interaction with liver sinusoidal endothelium inhibits organ-specific antitumor immunity through interleukin-1-induced mannose receptor in mice. Hepatology. 51:2172–2182. 2010. View Article : Google Scholar
13	Alexiou D, Karayiannakis AJ, Syrigos KN, Zbar A, Kremmyda A, Bramis I and Tsigris C: Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery. Eur J Cancer. 37:2392–2397. 2001. View Article : Google Scholar
14	Maeda K, Kang SM, Sawada T, Nishiguchi Y, Yashiro M, Ogawa Y, et al: Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer. Oncol Rep. 9:511–514. 2002.PubMed/NCBI
15	Mantur M, Snarska J, Koper O, Dzieciol J, Plonski A and Lemancewicz D: Serum sICAM, sVCAM and sE-selectin levels in colorectal cancer patients. Folia Histochem Cytobiol. 47:621–625. 2009.PubMed/NCBI
16	Taglia L, Matusiak D, Matkowskyj KA and Benya RV: Gastrin-releasing peptide mediates its morphogenic properties in human colon cancer by upregulating intracellular adhesion protein-1 (ICAM-1) via focal adhesion kinase. Am J Physiol Gastrointest Liver Physiol. 292:G182–G190. 2007. View Article : Google Scholar
17	Wimmenauer S, Keller H, Rückauer KD, Rahner S, Wolff-Vorbeck G, Kirste G, et al: Expression of CD44, ICAM-1 and N-CAM in colorectal cancer. Correlation with the tumor stage and the phenotypical characteristics of tumor-infiltrating lymphocytes. Anticancer Res. 17:2395–2400. 1997.
18	Kitagawa T, Matsumoto K and Iriyama K: Serum cell adhesion molecules in patients with colorectal cancer. Surg Today. 28:262–267. 1998. View Article : Google Scholar : PubMed/NCBI
19	Sanchez-Rovira P, Jimenez E, Carracedo J, Barneto IC, Ramirez R and Aranda E: Serum levels of intercellular adhesion molecule 1 (ICAM-1) in patients with colorectal cancer: inhibitory effect on cytotoxicity. Eur J Cancer. 34:394–398. 1998. View Article : Google Scholar : PubMed/NCBI
20	Kang X, Wang F, Xie JD, Cao J and Xian PZ: Clinical evaluation of serum concentrations of intercellular adhesion molecule-1 in patients with colorectal cancer. World J Gastroenterol. 11:4250–4253. 2005.PubMed/NCBI
21	Alexiou D, Karayiannakis AJ, Syrigos KN, Zbar A, Sekara E, Michail P, et al: Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients. Am J Gastroenterol. 98:478–485. 2003. View Article : Google Scholar : PubMed/NCBI
22	Nakata B, Hori T, Sunami T, Ogawa Y, Yashiro M, Maeda K, et al: Clinical significance of serum soluble intercellular adhesion molecule 1 in gastric cancer. Clin Cancer Res. 6:1175–1179. 2000.PubMed/NCBI
23	Zhang GJ and Adachi I: Serum levels of soluble intercellular adhesion molecule-1 and E-selectin in metastatic breast carcinoma: Correlations with clinicopathological features and prognosis. Int J Oncol. 14:71–77. 1999.
24	O'Hanlon DM, Fitzsimons H, Lynch J, Tormey S, Malone C and Given HF: Soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1) in breast carcinoma. Eur J Cancer. 38:2252–2257. 2002. View Article : Google Scholar
25	Silva HC, Garcao F, Coutinho EC, De Oliveira CF and Regateiro FJ: Soluble VCAM-1 and E-selectin in breast cancer: relationship with staging and with the detection of circulating cancer cells. Neoplasma. 53:538–543. 2006.PubMed/NCBI
26	Perabo F, Sharma S, Gierer R, Wirger A, Fimmers R, Steiner G, et al: Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies. Indian J Cancer. 38:1–7. 2001.PubMed/NCBI
27	Harning R, Mainolfi E, Bystryn JC, Henn M, Merluzzi VJ and Rothlein R: Serum levels of circulating intercellular adhesion molecule 1 in human malignant melanoma. Cancer Res. 51:5003–5005. 1991.PubMed/NCBI
28	Grothey A, Heistermann P, Philippou S and Voigtmann R: Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in patients with non-small-cell lung cancer: correlation with histological expression of ICAM-1 and tumour stage. Br J Cancer. 77:801–807. 1998. View Article : Google Scholar
29	Shimizu Y, Minemura M, Tsukishiro T, Kashii Y, Miyamoto M, Nishimori H, et al: Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis. Hepatology. 22:525–531. 1995.PubMed/NCBI
30	Christiansen I, Sundström C and Tötterman TH: Elevated serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia. Br J Haematol. 103:1129–1137. 1998. View Article : Google Scholar
31	Jackson AM, Alexandrov AB, Gribben SC, Esuvarnathan K and James K: Expression and shedding of ICAM-1 in bladder cancer and its immunotherapy. Int J Cancer. 55:921–925. 1993. View Article : Google Scholar : PubMed/NCBI
32	Budnik A, Grewe M, Gyufko K and Krutmann J: Analysis of the production of soluble ICAM-1 molecules by human cells. Exp Hematol. 24:352–359. 1996.PubMed/NCBI
33	Franzke A, Probst-Kepper M, Buer J, Duensing S, Hoffmann R, Wittke F, et al: Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma. Br J Cancer. 78:40–45. 1998. View Article : Google Scholar
34	Schellerer VS, Croner RS, Weinländer K, Hohenberger W, Stürzl M and Naschberger E: Endothelial cells of human colorectal cancer and healthy colon reveal phenotypic differences in culture. Lab Invest. 87:1159–1170. 2007. View Article : Google Scholar : PubMed/NCBI
35	Desmoulière A, Guyot C and Gabbiani G: The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol. 48:509–517. 2004.PubMed/NCBI
36	Gonda TA, Varro A, Wang TC and Tycko B: Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy? Semin Cell Dev Biol. 21:2–10. 2010. View Article : Google Scholar : PubMed/NCBI