Top

Published in:

01-04-2013 | Research Paper

Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer

Authors: Yoshinaga Okugawa, Yasuhiro Inoue, Koji Tanaka, Mikio Kawamura, Susumu Saigusa, Yuji Toiyama, Masaki Ohi, Keiichi Uchida, Yasuhiko Mohri, Masato Kusunoki

Published in: Clinical & Experimental Metastasis | Issue 4/2013

Abstract

Smad interacting protein 1 (SIP1) is an epithelial–mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA levels of SIP1 and other EMT regulators by real-time reverse transcription PCR in gastric tissue samples of 134 gastric cancer patients, and in five gastric cancer cell lines. SIP1 gene knockdown by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cells. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa. Although the mRNA expression of the other EMT regulators tested (Snail, Slug, and Twist) was not correlated with clinicopathological factors, increased SIP1 expression was an independent prognostic factor and an independent risk factor for peritoneal dissemination. In addition, SIP1 expression was significantly positive and correlated with vimentin expression. For intestinal type gastric cancer in particular, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p < 0.05). In vitro, cell proliferation, migration, invasion, and resistance to anoikis were significantly inhibited in SIP1 siRNA-transfected MKN7 cells compared to control siRNA. SIP1 appears to play an important role in progression to peritoneal carcinomatosis and may be a therapeutic target for patients with intestinal type gastric cancer.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics. CA Cancer J Clin 59(4):225–249. doi:10.3322/caac.20006 PubMedCrossRef

Maehara Y, Moriguchi S, Kakeji Y, Kohnoe S, Korenaga D, Haraguchi M, Sugimachi K (1991) Pertinent risk factors and gastric carcinoma with synchronous peritoneal dissemination or liver metastasis. Surgery 110(5):820–823PubMed

Moriguchi S, Maehara Y, Korenaga D, Sugimachi K, Nose Y (1992) Risk factors which predict pattern of recurrence after curative surgery for patients with advanced gastric cancer. Surg Oncol 1(5):341–346PubMedCrossRef

Duarte ILO (1981) Patterns of metastases in intestinal and diffuse types of carcinoma of the stomach. Hum Pathol 12:237–242PubMedCrossRef

Motoori M, Takemasa I, Doki Y, Saito S, Miyata H, Takiguchi S, Fujiwara Y, Yasuda T, Yano M, Kurokawa Y, Komori T, Yamasaki M, Ueno N, Oba S, Ishii S, Monden M, Kato K (2006) Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site. Eur J Cancer 42(12):1897–1903. doi:10.1016/j.ejca.2006.04.007 PubMedCrossRef

Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 7(2):131–142. doi:10.1038/nrm1835 PubMedCrossRef

Thiery JP (2003) Epithelial–mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 15(6):740–746PubMedCrossRef

Allan GJ, Beattie J, Flint DJ (2008) Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving IGF-binding protein-5. J Endocrinol 199(2):155–164. doi:10.1677/JOE-08-0269 PubMedCrossRef

Sleeman JP (2000) The lymph node as a bridgehead in the metastatic dissemination of tumors. Recent Results Cancer Res 157:55–81PubMedCrossRef

10.

Christiansen JJ, Rajasekaran AK (2006) Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res 66(17):8319–8326. doi:10.1158/0008-5472.CAN-06-0410 PubMedCrossRef

11.

Klymkowsky MW, Savagner P (2009) Epithelial–mesenchymal transition: a cancer researcher’s conceptual friend and foe. Am J Pathol 174(5):1588–1593. doi:10.2353/ajpath.2009.080545 PubMedCrossRef

12.

Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, van Roy F (2001) The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 7(6):1267–1278PubMedCrossRef

13.

Vandewalle C, Comijn J, De Craene B, Vermassen P, Bruyneel E, Andersen H, Tulchinsky E, Van Roy F, Berx G (2005) SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell–cell junctions. Nucleic Acids Res 33(20):6566–6578. doi:10.1093/nar/gki965 PubMedCrossRef

14.

Elloul S, Elstrand MB, Nesland JM, Trope CG, Kvalheim G, Goldberg I, Reich R, Davidson B (2005) Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer 103(8):1631–1643PubMedCrossRef

15.

Rodenhiser DI, Andrews J, Kennette W, Sadikovic B, Mendlowitz A, Tuck AB, Chambers AF (2008) Epigenetic mapping and functional analysis in a breast cancer metastasis model using whole-genome promoter tiling microarrays. Breast Cancer Res 10(4):R62. doi:10.1186/bcr2121 PubMedCrossRef

16.

Miyoshi A, Kitajima Y, Sumi K, Sato K, Hagiwara A, Koga Y, Miyazaki K (2004) Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells. Br J Cancer 90(6):1265–1273. doi:10.1038/sj.bjc.6601685 PubMedCrossRef

17.

Sakamoto K, Imanishi Y, Tomita T, Shimoda M, Kameyama K, Shibata K, Sakai N, Ozawa H, Shigetomi S, Fujii R, Fujii M, Ogawa K (2011) Overexpression of SIP1 and downregulation of E-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy. Ann Surg Oncol. doi:10.1245/s10434-011-2052-1

18.

Maeda G, Chiba T, Okazaki M, Satoh T, Taya Y, Aoba T, Kato K, Kawashiri S, Imai K (2005) Expression of SIP1 in oral squamous cell carcinomas: implications for E-cadherin expression and tumor progression. Int J Oncol 27(6):1535–1541PubMed

19.

Kahlert C, Lahes S, Radhakrishnan P, Dutta S, Mogler C, Herpel E, Brand K, Steinert G, Schneider M, Mollenhauer M, Reissfelder C, Klupp F, Fritzmann J, Wunder C, Benner A, Kloor M, Huth C, Contin P, Ulrich A, Koch M, Weitz J (2011) Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro. Clin Cancer Res 17(24):7654–7663. doi:10.1158/1078-0432.CCR-10-2816 PubMedCrossRef

20.

Toiyama Y, Inoue Y, Yasuda H, Saigusa S, Yokoe T, Okugawa Y, Tanaka K, Miki C, Kusunoki M (2011) DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness. J Gastroenterol 46(2):153–163. doi:10.1007/s00535-010-0318-1 PubMedCrossRef

21.

Eccles SA, Welch DR (2007) Metastasis: recent discoveries and novel treatment strategies. Lancet 369(9574):1742–1757. doi:10.1016/S0140-6736(07)60781-8 PubMedCrossRef

22.

Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49PubMed

23.

Yuasa Y (2003) Control of gut differentiation and intestinal-type gastric carcinogenesis. Nat Rev Cancer 3(8):592–600. doi:10.1038/nrc1141 PubMedCrossRef

24.

Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7(6):415–428. doi:10.1038/nrc2131 PubMedCrossRef

25.

Imamichi Y, Konig A, Gress T, Menke A (2007) Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer. Oncogene 26(16):2381–2385. doi:10.1038/sj.onc.1210012 PubMedCrossRef

26.

Ohta H, Aoyagi K, Fukaya M, Danjoh I, Ohta A, Isohata N, Saeki N, Taniguchi H, Sakamoto H, Shimoda T, Tani T, Yoshida T, Sasaki H (2009) Cross talk between hedgehog and epithelial–mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers. Br J Cancer 100(2):389–398. doi:10.1038/sj.bjc.6604846 PubMedCrossRef

27.

Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Hofler H, Becker KF (2002) Differential expression of the epithelial–mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol 161(5):1881–1891. doi:10.1016/S0002-9440(10)64464-1 PubMedCrossRef

28.

Shino Y, Watanabe A, Yamada Y, Tanase M, Yamada T, Matsuda M, Yamashita J, Tatsumi M, Miwa T, Nakano H (1995) Clinicopathologic evaluation of immunohistochemical E-cadherin expression in human gastric carcinomas. Cancer 76(11):2193–2201PubMedCrossRef

29.

Yonemura Y, Endou Y, Kimura K, Fushida S, Bandou E, Taniguchi K, Kinoshita K, Ninomiya I, Sugiyama K, Heizmann CW, Schafer BW, Sasaki T (2000) Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer. Clin Cancer Res 6(11):4234–4242PubMed

30.

Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, van Beijnum JR, Griffioen AW, Vink J, Krimpenfort P, Peterse JL, Cardiff RD, Berns A, Jonkers J (2006) Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 10(5):437–449. doi:10.1016/j.ccr.2006.09.013 PubMedCrossRef

31.

Smit MA, Geiger TR, Song JY, Gitelman I, Peeper DS (2009) A Twist–Snail axis critical for TrkB-induced epithelial–mesenchymal transition-like transformation, anoikis resistance, and metastasis. Mol Cell Biol 29(13):3722–3737. doi:10.1128/MCB.01164-08 PubMedCrossRef

32.

Landen CN, Merritt WM, Mangala LS, Sanguino AM, Bucana C, Lu C, Lin YG, Han LY, Kamat AA, Schmandt R, Coleman RL, Gershenson DM, Lopez-Berestein G, Sood AK (2006) Intraperitoneal delivery of liposomal siRNA for therapy of advanced ovarian cancer. Cancer Biol Ther 5(12):1708–1713PubMedCrossRef

33.

Inoue M, Matsumoto S, Saito H, Tsujitani S, Ikeguchi M (2008) Intraperitoneal administration of a small interfering RNA targeting nuclear factor-kappa B with paclitaxel successfully prolongs the survival of xenograft model mice with peritoneal metastasis of gastric cancer. Int J Cancer 123(11):2696–2701. doi:10.1002/ijc.23867 PubMedCrossRef

Title: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer
Authors: Yoshinaga Okugawa
Yasuhiro Inoue
Koji Tanaka
Mikio Kawamura
Susumu Saigusa
Yuji Toiyama
Masaki Ohi
Keiichi Uchida
Yasuhiko Mohri
Masato Kusunoki
Publication date: 01-04-2013
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 4/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-012-9547-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2013

Dynamic analysis of lung metastasis by mouse osteosarcoma LM8: VEGF is a candidate for anti-metastasis therapy

Sex-dependent liver colonization of human melanoma in SCID mice—role of host defense mechanisms

Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors

Liver-directed chemotherapy of cetuximab and bevacizumab in combination with oxaliplatin is more effective to inhibit tumor growth of CC531 colorectal rat liver metastases than systemic chemotherapy

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of intrathoracic lymph node metastases from extrathoracic malignancies

Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus

Keynote webinar | Spotlight on antibody–drug conjugates in cancer