Skip to main content
Erschienen in: Tumor Biology 5/2016

27.11.2015 | Research Article

Wnt5a and Ror2 expression associate with the disease progress of primary thyroid lymphoma

verfasst von: Lei Wang, Dong Yang, Ying-Hou Wang, Xi Li, Hong-Ming Gao, Jun-Yuan Lv, Lei Wang, Shi-Jie Xin

Erschienen in: Tumor Biology | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

Primary thyroid lymphoma (PTL) is a rare malignant thyroid tumor; its pathogenesis is closely related to chronic lymphocytic thyroiditis. The different pathological subtypes and stages of PTL have distinct clinical characteristics and prognosis, but the specific reasons are not clear. Wnt5a is a representative protein of non-canonical Wnt signaling. It plays an important role in many different types of tumors. This study is to explore the changes of Wnt5a and its receptor Ror2 in PTL development process and the clinical significance of their represent. We collected 22 PTL patient tumor specimens and clinical data. We observed the expression of Wnt5a and Ror2 in PTL tumor tissues by immunohistochemistry. Wnt5a was expressed positively in 12 (54.5 %) cases, and Ror2 was expressed positively in 18 (81.8 %) cases. The expression of Wnt5a had a significant difference in different pathological subtypes of PTL (P < 0.05). Wnt5a and Ror2 expression were associated with local invasion and clinical stage, respectively (P < 0.05), and had no significant correlation with age, gender, and tumor size. Although, no significant difference in overall survival was found between positive and negative groups of Wnt5a (P = 0.416) or Ror2 (P = 0.256), respectively. We still consider that Wnt5a and Ror2 play a complex and subtle role in the pathogenesis and progression of PTL and may become potential biomarkers and therapeutic targets of PTL.
Literatur
1.
Zurück zum Zitat Ansell SM, Grant CS, Habermann TM. Primary thyroid lymphoma. Semin Oncol. 1999;26:316–23.PubMed Ansell SM, Grant CS, Habermann TM. Primary thyroid lymphoma. Semin Oncol. 1999;26:316–23.PubMed
2.
Zurück zum Zitat Pedersen RK, Pedersen NT. Primary non-Hodgkin’s lymphoma of the thyroid gland: a population based study. Histopathology. 1996;28(1):25–32.CrossRefPubMed Pedersen RK, Pedersen NT. Primary non-Hodgkin’s lymphoma of the thyroid gland: a population based study. Histopathology. 1996;28(1):25–32.CrossRefPubMed
3.
Zurück zum Zitat Hwang YC, Kim TY, Kim WB, et al. Clinical characteristics of primary thyroid lymphoma in Koreans. Endocr J. 2009;56(3):399–405.CrossRefPubMed Hwang YC, Kim TY, Kim WB, et al. Clinical characteristics of primary thyroid lymphoma in Koreans. Endocr J. 2009;56(3):399–405.CrossRefPubMed
4.
Zurück zum Zitat Graff-Baker A, Roman SA, Thomas DC. Prognosis of primary thyroid lymphoma: demographic, clinical and pathologic predictors of survival in 1408 cases. Surgery. 2009;146(6):1105–15.CrossRefPubMed Graff-Baker A, Roman SA, Thomas DC. Prognosis of primary thyroid lymphoma: demographic, clinical and pathologic predictors of survival in 1408 cases. Surgery. 2009;146(6):1105–15.CrossRefPubMed
5.
6.
Zurück zum Zitat Kossev P, Livolsi V. Lymphoid lesions of the thyroid: review in light of the revised European American lymphoma classification and upcoming World Health Organization classification. Thyroid. 1999;9:1273–80.CrossRefPubMed Kossev P, Livolsi V. Lymphoid lesions of the thyroid: review in light of the revised European American lymphoma classification and upcoming World Health Organization classification. Thyroid. 1999;9:1273–80.CrossRefPubMed
7.
Zurück zum Zitat Katna R, Shet T, Sengar M. Clinicopathologic study and outcome analysis of thyroid lymphomas: experience from a tertiary cancer center. Head Neck. 2013;35(2):165–71.CrossRefPubMed Katna R, Shet T, Sengar M. Clinicopathologic study and outcome analysis of thyroid lymphomas: experience from a tertiary cancer center. Head Neck. 2013;35(2):165–71.CrossRefPubMed
8.
Zurück zum Zitat Sakorafas GH, Kokkoris P, Farley DR. Primary thyroid lymphoma (correction of lympoma): diagnostic and therapeutic dilemmas. Surg Oncol. 2010;19(4):e124–9.CrossRefPubMed Sakorafas GH, Kokkoris P, Farley DR. Primary thyroid lymphoma (correction of lympoma): diagnostic and therapeutic dilemmas. Surg Oncol. 2010;19(4):e124–9.CrossRefPubMed
9.
Zurück zum Zitat Cha H, Kim JW, Suh CO. Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study. Radiat Oncol J. 2013;31(4):177–84.CrossRefPubMedPubMedCentral Cha H, Kim JW, Suh CO. Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study. Radiat Oncol J. 2013;31(4):177–84.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Ruggiero FP, Frauenhoffer E, Stack BC. Thyroid lymphoma: a single institution’s experience. Otolaryngol Head Neck Surg. 2005;133:888–96.CrossRefPubMed Ruggiero FP, Frauenhoffer E, Stack BC. Thyroid lymphoma: a single institution’s experience. Otolaryngol Head Neck Surg. 2005;133:888–96.CrossRefPubMed
11.
Zurück zum Zitat Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.CrossRefPubMed Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.CrossRefPubMed
12.
Zurück zum Zitat Verkaar F, Zaman GJ. A model for signaling specificity of Wnt/Frizzled combinations through co-receptor recruitment. FEBS Lett. 2010;584(18):3850–4.CrossRefPubMed Verkaar F, Zaman GJ. A model for signaling specificity of Wnt/Frizzled combinations through co-receptor recruitment. FEBS Lett. 2010;584(18):3850–4.CrossRefPubMed
13.
Zurück zum Zitat Pukrop T, Klemm F, Hagemann T, et al. Wnt5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci U S A. 2006;103:5454–9.CrossRefPubMedPubMedCentral Pukrop T, Klemm F, Hagemann T, et al. Wnt5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci U S A. 2006;103:5454–9.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat O’Connell MP, Fiori JL, Xu M, et al. The orphan tyrosine kinase receptor, Ror2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 2010;29:34–44.CrossRefPubMed O’Connell MP, Fiori JL, Xu M, et al. The orphan tyrosine kinase receptor, Ror2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 2010;29:34–44.CrossRefPubMed
15.
Zurück zum Zitat Ripka S, Konig A, Buchholz M, et al. WNT5A—target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer. Carcinogenesis. 2007;28:1178–87.CrossRefPubMed Ripka S, Konig A, Buchholz M, et al. WNT5A—target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer. Carcinogenesis. 2007;28:1178–87.CrossRefPubMed
16.
Zurück zum Zitat Yamamoto H, Kitadai Y, Yamamoto H, et al. Laminin gamma2 mediates Wnt5a-induced invasion of gastric cancer cells. Gastroenterology. 2009;137(1):242–52. 252.e1-6.CrossRefPubMed Yamamoto H, Kitadai Y, Yamamoto H, et al. Laminin gamma2 mediates Wnt5a-induced invasion of gastric cancer cells. Gastroenterology. 2009;137(1):242–52. 252.e1-6.CrossRefPubMed
17.
Zurück zum Zitat Enomoto M, Hayakawa S, Itsukushima S, et al. Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling. Oncogene. 2009;28(36):3197–208.CrossRefPubMed Enomoto M, Hayakawa S, Itsukushima S, et al. Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling. Oncogene. 2009;28(36):3197–208.CrossRefPubMed
18.
Zurück zum Zitat He F, Xiong W, Yu X, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development. 2008;135:3871–9.CrossRefPubMedPubMedCentral He F, Xiong W, Yu X, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development. 2008;135:3871–9.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Kremenevskaja N, von Wasielewski R, Rao AS, et al. Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene. 2005;24(13):2144–54.CrossRefPubMed Kremenevskaja N, von Wasielewski R, Rao AS, et al. Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene. 2005;24(13):2144–54.CrossRefPubMed
21.
Zurück zum Zitat Han X, Kilfoy B, Zheng T, et al. Lymphoma survival patterns by WHO subtype in the United States, 1973–2003. Cancer Causes Control. 2008;19:841–58.CrossRefPubMed Han X, Kilfoy B, Zheng T, et al. Lymphoma survival patterns by WHO subtype in the United States, 1973–2003. Cancer Causes Control. 2008;19:841–58.CrossRefPubMed
22.
Zurück zum Zitat Thieblemont C, Mayer A, Dumontet C, et al. Primary thyroid lymphoma is a heterogeneous disease. J Clin Endocrinol Metab. 2002;87(1):105–11.CrossRefPubMed Thieblemont C, Mayer A, Dumontet C, et al. Primary thyroid lymphoma is a heterogeneous disease. J Clin Endocrinol Metab. 2002;87(1):105–11.CrossRefPubMed
23.
Zurück zum Zitat Grivennikov SI, Karin M. Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev. 2010;20(1):65–71.CrossRefPubMed Grivennikov SI, Karin M. Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev. 2010;20(1):65–71.CrossRefPubMed
24.
Zurück zum Zitat Mikels AJ, Nusse R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 2006;4(4):e115.CrossRefPubMedPubMedCentral Mikels AJ, Nusse R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 2006;4(4):e115.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Kim J, Kim DW, Chang W, et al. Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-κB-B cell lymphoma 6 signaling. J Immunol. 2012;188(1):182–9.CrossRefPubMed Kim J, Kim DW, Chang W, et al. Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-κB-B cell lymphoma 6 signaling. J Immunol. 2012;188(1):182–9.CrossRefPubMed
26.
Zurück zum Zitat Lee JM, Kim IS, Kim H, et al. RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer. Mol Cell. 2010;37(2):183–95.CrossRefPubMed Lee JM, Kim IS, Kim H, et al. RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer. Mol Cell. 2010;37(2):183–95.CrossRefPubMed
27.
Zurück zum Zitat Topol L, Jiang X, Choi H, et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation. J Cell Biol. 2003;162(5):899–908.CrossRefPubMedPubMedCentral Topol L, Jiang X, Choi H, et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation. J Cell Biol. 2003;162(5):899–908.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Sato A, Yamamoto H, Sakane H, et al. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29(1):41–54.CrossRefPubMed Sato A, Yamamoto H, Sakane H, et al. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29(1):41–54.CrossRefPubMed
29.
Zurück zum Zitat Blanc E, Roux GL, Bénard J, et al. Low expression of Wnt-5a gene is associated with high-risk neuroblastoma. Oncogene. 2005;24(7):1277–83.CrossRefPubMed Blanc E, Roux GL, Bénard J, et al. Low expression of Wnt-5a gene is associated with high-risk neuroblastoma. Oncogene. 2005;24(7):1277–83.CrossRefPubMed
30.
Zurück zum Zitat Leris AC, Roberts TR, Jiang WG, et al. WNT5A expression in human breast cancer. Anticancer Res. 2005;25(2A):731–4.PubMed Leris AC, Roberts TR, Jiang WG, et al. WNT5A expression in human breast cancer. Anticancer Res. 2005;25(2A):731–4.PubMed
31.
Zurück zum Zitat Weeraratna AT, Jiang Y, Hostetter G, et al. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 2002;1(3):279–88.CrossRefPubMed Weeraratna AT, Jiang Y, Hostetter G, et al. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 2002;1(3):279–88.CrossRefPubMed
32.
Zurück zum Zitat Da Forno PD, Pringle JH, Hutchinson P, et al. WNT5A expression increases during melanoma progression and correlates with outcome. Clin Cancer Res. 2008;14(18):5825–32.CrossRefPubMed Da Forno PD, Pringle JH, Hutchinson P, et al. WNT5A expression increases during melanoma progression and correlates with outcome. Clin Cancer Res. 2008;14(18):5825–32.CrossRefPubMed
33.
Zurück zum Zitat Liang H, Chen Q, Coles AH, et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell. 2003;4(5):349–60.CrossRefPubMed Liang H, Chen Q, Coles AH, et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell. 2003;4(5):349–60.CrossRefPubMed
34.
Zurück zum Zitat Nishita M, Yoo SK, Nomachi A, et al. Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration. J Cell Biol. 2006;175(4):555–62.CrossRefPubMedPubMedCentral Nishita M, Yoo SK, Nomachi A, et al. Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration. J Cell Biol. 2006;175(4):555–62.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Yamamoto S, Nishimura O, Misaki K, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15(1):23–36.CrossRefPubMed Yamamoto S, Nishimura O, Misaki K, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15(1):23–36.CrossRefPubMed
36.
Zurück zum Zitat Grumolato L, Liu G, Mong P, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24(22):2517–30.CrossRefPubMedPubMedCentral Grumolato L, Liu G, Mong P, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24(22):2517–30.CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Wright TM, Brannon AR, Gordan JD, et al. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene. 2009;28(27):2513–23.CrossRefPubMedPubMedCentral Wright TM, Brannon AR, Gordan JD, et al. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene. 2009;28(27):2513–23.CrossRefPubMedPubMedCentral
38.
Metadaten
Titel
Wnt5a and Ror2 expression associate with the disease progress of primary thyroid lymphoma
verfasst von
Lei Wang
Dong Yang
Ying-Hou Wang
Xi Li
Hong-Ming Gao
Jun-Yuan Lv
Lei Wang
Shi-Jie Xin
Publikationsdatum
27.11.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4470-3

Weitere Artikel der Ausgabe 5/2016

Tumor Biology 5/2016 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.