Skip to main content
Erschienen in: Cellular Oncology 5/2018

15.06.2018 | Original Paper

Stromal collagen type VI associates with features of malignancy and predicts poor prognosis in salivary gland cancer

verfasst von: Linus Angenendt, Jan-Henrik Mikesch, Dennis Görlich, Alina Busch, Irina Arnhold, Claudia Rudack, Wolfgang Hartmann, Eva Wardelmann, Wolfgang E. Berdel, Markus Stenner, Christoph Schliemann, Inga Grünewald

Erschienen in: Cellular Oncology | Ausgabe 5/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Collagen Type VI (COLVI) is an extracellular matrix protein that is upregulated in various solid tumours during tumour progression and has been shown to stimulate proliferation, suppress apoptosis and promote invasion and metastasis. It has also been described as a mediator of chemotherapy resistance and as a therapeutic target in preclinical cancer models. Here, we aimed to analyse the prognostic role of COLVI in salivary gland cancer (SGC).

Methods

Stromal COLVI protein expression was assessed in primary SGC specimens of 91 patients using immunohistochemistry (IHC). The IHC expression patterns obtained were subsequently correlated with various survival and clinicopathological features, including Ki-67 and p53 expression.

Results

We found that COLVI was expressed in all SGC specimens. High expression was found to be associated with features of malignancy such as high histologic grades, advanced and invasive T stages and metastatic lymph node involvement (p < 0.05 for all variables). COLVI expression was also found to correlate with both Ki-67 and p53 expression (p < 0.01). We found that high COLVI expression predicted a significantly inferior 5-year overall survival (38.3%, 55.1% and 93.8%; p = 0.002) and remained a significant predictor of prognosis in a multivariate Cox regression analysis (hazard ratio, 2.62; 95% confidence interval, 1.22–5.61; p = 0.013). In all low-risk subgroups COLVI expression identified patients with an adverse outcome. Patients receiving adjuvant radiotherapy had a poor survival when expressing high levels of COLVI.

Conclusions

Our data indicate that stromal COLVI expression associates with key features of malignancy, represents a novel independent prognostic factor and may affect response to radiotherapy in SGC. Although our results warrant validation in an independent cohort, assessing stromal COLVI expression may be suitable for future diagnostic and therapeutic decision making in patients with SGC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat J.W. Everson, P. Auclair, D.R. Gnepp, A.K. El-Naggar, in WHO Classification of Head and Neck Tumours. Tumours of the salivary glands (IARCPress, 2005) J.W. Everson, P. Auclair, D.R. Gnepp, A.K. El-Naggar, in WHO Classification of Head and Neck Tumours. Tumours of the salivary glands (IARCPress, 2005)
2.
Zurück zum Zitat V.V. Poorten, A. Hart, T. Vauterin, G. Jeunen, J. Schoenaers, M. Hamoir, A. Balm, E. Stennert, O. Guntinas-Lichius, P. Delaere, Prognostic index for patients with parotid carcinoma: International external validation in a Belgian-German database. Cancer 115, 540–550 (2009). https://doi.org/10.1002/cncr.24015 CrossRefPubMed V.V. Poorten, A. Hart, T. Vauterin, G. Jeunen, J. Schoenaers, M. Hamoir, A. Balm, E. Stennert, O. Guntinas-Lichius, P. Delaere, Prognostic index for patients with parotid carcinoma: International external validation in a Belgian-German database. Cancer 115, 540–550 (2009). https://​doi.​org/​10.​1002/​cncr.​24015 CrossRefPubMed
6.
Zurück zum Zitat M. Nagliati, A. Bolner, V. Vanoni, L. Tomio, G. Lay, R. Murtas, M.A. Deidda, A. Madeddu, E. Delmastro, R. Verna, P. Gabriele, M. Amichetti, Surgery and radiotherapy in the treatment of malignant parotid tumors: A retrospective multicenter study. Tumori 95, 442–448 (2009)CrossRefPubMed M. Nagliati, A. Bolner, V. Vanoni, L. Tomio, G. Lay, R. Murtas, M.A. Deidda, A. Madeddu, E. Delmastro, R. Verna, P. Gabriele, M. Amichetti, Surgery and radiotherapy in the treatment of malignant parotid tumors: A retrospective multicenter study. Tumori 95, 442–448 (2009)CrossRefPubMed
9.
Zurück zum Zitat A. Amini, T.V. Waxweiler, J.V. Brower, B.L. Jones, J.D. McDermott, D. Raben, D. Ghosh, D.W. Bowles, S.D. Karam, Association of adjuvant chemoradiotherapy vs radiotherapy alone with survival in patients with resected major salivary gland carcinoma: Data from the national cancer data base. JAMA Otolaryngol Head Neck Surg 142, 1100–1110 (2016). https://doi.org/10.1001/jamaoto.2016.2168 CrossRefPubMed A. Amini, T.V. Waxweiler, J.V. Brower, B.L. Jones, J.D. McDermott, D. Raben, D. Ghosh, D.W. Bowles, S.D. Karam, Association of adjuvant chemoradiotherapy vs radiotherapy alone with survival in patients with resected major salivary gland carcinoma: Data from the national cancer data base. JAMA Otolaryngol Head Neck Surg 142, 1100–1110 (2016). https://​doi.​org/​10.​1001/​jamaoto.​2016.​2168 CrossRefPubMed
13.
Zurück zum Zitat L. Angenendt, S. Reuter, D. Kentrup, A.S. Benk, F. Neumann, J. Huve, A.C. Martens, C. Schwoppe, T. Kessler, L.H. Schmidt, T. Sauer, C. Brand, J.H. Mikesch, G. Lenz, R.M. Mesters, C. Muller-Tidow, W. Hartmann, E. Wardelmann, D. Neri, W.E. Berdel, C. Roesli, C. Schliemann, An atlas of bloodstream-accessible bone marrow proteins for site-directed therapy of acute myeloid leukemia. Leukemia 32, 510–519 (2018). https://doi.org/10.1038/leu.2017.208 CrossRefPubMed L. Angenendt, S. Reuter, D. Kentrup, A.S. Benk, F. Neumann, J. Huve, A.C. Martens, C. Schwoppe, T. Kessler, L.H. Schmidt, T. Sauer, C. Brand, J.H. Mikesch, G. Lenz, R.M. Mesters, C. Muller-Tidow, W. Hartmann, E. Wardelmann, D. Neri, W.E. Berdel, C. Roesli, C. Schliemann, An atlas of bloodstream-accessible bone marrow proteins for site-directed therapy of acute myeloid leukemia. Leukemia 32, 510–519 (2018). https://​doi.​org/​10.​1038/​leu.​2017.​208 CrossRefPubMed
15.
Zurück zum Zitat P. Iyengar, T.P. Combs, S.J. Shah, V. Gouon-Evans, J.W. Pollard, C. Albanese, L. Flanagan, M.P. Tenniswood, C. Guha, M.P. Lisanti, R.G. Pestell, P.E. Scherer, Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 22, 6408–6423 (2003). https://doi.org/10.1038/sj.onc.1206737 CrossRefPubMed P. Iyengar, T.P. Combs, S.J. Shah, V. Gouon-Evans, J.W. Pollard, C. Albanese, L. Flanagan, M.P. Tenniswood, C. Guha, M.P. Lisanti, R.G. Pestell, P.E. Scherer, Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 22, 6408–6423 (2003). https://​doi.​org/​10.​1038/​sj.​onc.​1206737 CrossRefPubMed
18.
Zurück zum Zitat J. Han, J.C. Daniel, Biosynthesis of type VI collagen by glioblastoma cells and possible function in cell invasion of three-dimensional matrices. Connect Tissue Res 31, 161–170 (1995)CrossRefPubMed J. Han, J.C. Daniel, Biosynthesis of type VI collagen by glioblastoma cells and possible function in cell invasion of three-dimensional matrices. Connect Tissue Res 31, 161–170 (1995)CrossRefPubMed
20.
Zurück zum Zitat M. Schnoor, P. Cullen, J. Lorkowski, K. Stolle, H. Robenek, D. Troyer, J. Rauterberg, S. Lorkowski, Production of type VI collagen by human macrophages: A new dimension in macrophage functional heterogeneity. J Immunol 180, 5707–5719 (2008)CrossRefPubMed M. Schnoor, P. Cullen, J. Lorkowski, K. Stolle, H. Robenek, D. Troyer, J. Rauterberg, S. Lorkowski, Production of type VI collagen by human macrophages: A new dimension in macrophage functional heterogeneity. J Immunol 180, 5707–5719 (2008)CrossRefPubMed
23.
Zurück zum Zitat R.R. Varma, S.M. Hector, K. Clark, W.R. Greco, L. Hawthorn, L. Pendyala, Gene expression profiling of a clonal isolate of oxaliplatin-resistant ovarian carcinoma cell line A2780/C10. Oncol Rep 14, 925–932 (2005)PubMed R.R. Varma, S.M. Hector, K. Clark, W.R. Greco, L. Hawthorn, L. Pendyala, Gene expression profiling of a clonal isolate of oxaliplatin-resistant ovarian carcinoma cell line A2780/C10. Oncol Rep 14, 925–932 (2005)PubMed
24.
Zurück zum Zitat P. Iyengar, V. Espina, T.W. Williams, Y. Lin, D. Berry, L.A. Jelicks, H. Lee, K. Temple, R. Graves, J. Pollard, N. Chopra, R.G. Russell, R. Sasisekharan, B.J. Trock, M. Lippman, V.S. Calvert, E.F. Petricoin 3rd, L. Liotta, E. Dadachova, R.G. Pestell, M.P. Lisanti, P. Bonaldo, P.E. Scherer, Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. J Clin Invest 115, 1163–1176 (2005). https://doi.org/10.1172/JCI23424 CrossRefPubMedPubMedCentral P. Iyengar, V. Espina, T.W. Williams, Y. Lin, D. Berry, L.A. Jelicks, H. Lee, K. Temple, R. Graves, J. Pollard, N. Chopra, R.G. Russell, R. Sasisekharan, B.J. Trock, M. Lippman, V.S. Calvert, E.F. Petricoin 3rd, L. Liotta, E. Dadachova, R.G. Pestell, M.P. Lisanti, P. Bonaldo, P.E. Scherer, Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. J Clin Invest 115, 1163–1176 (2005). https://​doi.​org/​10.​1172/​JCI23424 CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat S. Cattaruzza, P.A. Nicolosi, P. Braghetta, L. Pazzaglia, M.S. Benassi, P. Picci, K. Lacrima, D. Zanocco, E. Rizzo, W.B. Stallcup, A. Colombatti, R. Perris, NG2/CSPG4-collagen type VI interplays putatively involved in the microenvironmental control of tumour engraftment and local expansion. J Mol Cell Biol 5, 176–193 (2013). https://doi.org/10.1093/jmcb/mjt010 CrossRefPubMedPubMedCentral S. Cattaruzza, P.A. Nicolosi, P. Braghetta, L. Pazzaglia, M.S. Benassi, P. Picci, K. Lacrima, D. Zanocco, E. Rizzo, W.B. Stallcup, A. Colombatti, R. Perris, NG2/CSPG4-collagen type VI interplays putatively involved in the microenvironmental control of tumour engraftment and local expansion. J Mol Cell Biol 5, 176–193 (2013). https://​doi.​org/​10.​1093/​jmcb/​mjt010 CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat M.A. Burg, E. Tillet, R. Timpl, W.B. Stallcup, Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix molecules. J Biol Chem 271, 26110–26116 (1996)CrossRefPubMed M.A. Burg, E. Tillet, R. Timpl, W.B. Stallcup, Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix molecules. J Biol Chem 271, 26110–26116 (1996)CrossRefPubMed
28.
Zurück zum Zitat M. Chekenya, C. Krakstad, A. Svendsen, I.A. Netland, V. Staalesen, B.B. Tysnes, F. Selheim, J. Wang, P.O. Sakariassen, T. Sandal, P.E. Lonning, T. Flatmark, P.O. Enger, R. Bjerkvig, M. Sioud, W.B. Stallcup, The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene 27, 5182–5194 (2008). https://doi.org/10.1038/onc.2008.157 CrossRefPubMedPubMedCentral M. Chekenya, C. Krakstad, A. Svendsen, I.A. Netland, V. Staalesen, B.B. Tysnes, F. Selheim, J. Wang, P.O. Sakariassen, T. Sandal, P.E. Lonning, T. Flatmark, P.O. Enger, R. Bjerkvig, M. Sioud, W.B. Stallcup, The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene 27, 5182–5194 (2008). https://​doi.​org/​10.​1038/​onc.​2008.​157 CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat A. Urciuolo, M. Quarta, V. Morbidoni, F. Gattazzo, S. Molon, P. Grumati, F. Montemurro, F.S. Tedesco, B. Blaauw, G. Cossu, G. Vozzi, T.A. Rando, P. Bonaldo, Collagen VI regulates satellite cell self-renewal and muscle regeneration. Nat Commun 4, 1964 (2013). https://doi.org/10.1038/ncomms2964 A. Urciuolo, M. Quarta, V. Morbidoni, F. Gattazzo, S. Molon, P. Grumati, F. Montemurro, F.S. Tedesco, B. Blaauw, G. Cossu, G. Vozzi, T.A. Rando, P. Bonaldo, Collagen VI regulates satellite cell self-renewal and muscle regeneration. Nat Commun 4, 1964 (2013). https://​doi.​org/​10.​1038/​ncomms2964
34.
35.
Zurück zum Zitat D.G.K. Rasmussen, T.W. Hansen, B.J. von Scholten, S.H. Nielsen, H. Reinhard, H.H. Parving, M. Tepel, M.A. Karsdal, P.K. Jacobsen, F. Genovese, P. Rossing, Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria. Diabetes Care, dc172392 (2018). https://doi.org/10.2337/dc17-2392 CrossRefPubMed D.G.K. Rasmussen, T.W. Hansen, B.J. von Scholten, S.H. Nielsen, H. Reinhard, H.H. Parving, M. Tepel, M.A. Karsdal, P.K. Jacobsen, F. Genovese, P. Rossing, Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria. Diabetes Care, dc172392 (2018). https://​doi.​org/​10.​2337/​dc17-2392 CrossRefPubMed
39.
Zurück zum Zitat C. Schliemann, K.L. Gutbrodt, A. Kerkhoff, M. Pohlen, S. Wiebe, G. Silling, L. Angenendt, T. Kessler, R.M. Mesters, L. Giovannoni, M. Schafers, B. Altvater, C. Rossig, I. Grunewald, E. Wardelmann, G. Kohler, D. Neri, M. Stelljes, W.E. Berdel, Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Cancer Immunol Res 3, 547–556 (2015). https://doi.org/10.1158/2326-6066.CIR-14-0179 CrossRefPubMed C. Schliemann, K.L. Gutbrodt, A. Kerkhoff, M. Pohlen, S. Wiebe, G. Silling, L. Angenendt, T. Kessler, R.M. Mesters, L. Giovannoni, M. Schafers, B. Altvater, C. Rossig, I. Grunewald, E. Wardelmann, G. Kohler, D. Neri, M. Stelljes, W.E. Berdel, Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Cancer Immunol Res 3, 547–556 (2015). https://​doi.​org/​10.​1158/​2326-6066.​CIR-14-0179 CrossRefPubMed
Metadaten
Titel
Stromal collagen type VI associates with features of malignancy and predicts poor prognosis in salivary gland cancer
verfasst von
Linus Angenendt
Jan-Henrik Mikesch
Dennis Görlich
Alina Busch
Irina Arnhold
Claudia Rudack
Wolfgang Hartmann
Eva Wardelmann
Wolfgang E. Berdel
Markus Stenner
Christoph Schliemann
Inga Grünewald
Publikationsdatum
15.06.2018
Verlag
Springer Netherlands
Erschienen in
Cellular Oncology / Ausgabe 5/2018
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-018-0389-1

Weitere Artikel der Ausgabe 5/2018

Cellular Oncology 5/2018 Zur Ausgabe

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …

Personalisierte Medizin in der Onkologie

Aufgrund des erheblichen technologischen Fortschritts in der molekularen und genetischen Diagnostik sowie zunehmender Erkenntnisse über die molekulare Pathogenese von Krankheiten hat in den letzten zwei Jahrzehnten ein grundlegender …