Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells

Elisa Tramentozzi, Erlis Ruli, Imerio Angriman, Romeo Bardini, Michela Campora, Vincenza Guzzardo, Rita Zamarchi, Elisabetta Rossi, Massimo Rugge, Paola Finotti

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature of Grp94 is its translocation from the ER to the cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both the tumor pathology and anti-tumor therapy. We wanted to address the question of whether Grp94 could be measured as liquid marker in cancer patients in order to make predictions of diagnostic and therapeutic relevance for the tumor. To this aim, we performed an in-depth investigation on patients with primary tumors of the gastrointestinal (GI) tract, using different methodological approaches to detect Grp94 in tumor tissues, plasma and peripheral blood mononuclear cells (PBMCs). Results indicate that Grp94 is not only the antigen highly expressed in any tumor tissue and in cells of tumor infiltrates, mostly B lymphocytes, but it is also found in the circulation. However, the only form in which Grp94 was detected in the plasma of any patients and in B lymphocytes induced to proliferate, was that of stable complexes with Immunoglobulin (Ig)G. Using a specific immune-enzyme assay to measure plasma Grp94-IgG complexes, we showed that Grp94-IgG complexes were significantly increased in cancer patients compared to healthy control subjects, serving as diagnostic tumor biomarker. Results also demonstrate that the stimulation of patient PBMCs with Grp94-IgG complexes led to an increased secretion of inflammatory cytokines that might drive a potentially beneficial anti-tumor effect.

Original languageEnglish
Pages (from-to)72923-72940
Number of pages18
JournalOncotarget
Volume7
Issue number45
DOIs
Publication statusPublished - 2016

Fingerprint

Tumor Biomarkers
Blood Cells
Immunoglobulin G
Glucose
Neoplasms
Endoplasmic Reticulum
B-Lymphocytes
Enzyme Assays
Neoplasm Antigens
Heat-Shock Proteins
Gastrointestinal Tract
Healthy Volunteers
Pathology
Cytokines
Antigens

Keywords

  • Biomarkers
  • Gastrointestinal neoplasms
  • Heat shock Proteins
  • Immunoglobulins
  • Immunomodulation

ASJC Scopus subject areas

  • Oncology

Cite this

Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells. / Tramentozzi, Elisa; Ruli, Erlis; Angriman, Imerio; Bardini, Romeo; Campora, Michela; Guzzardo, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Rugge, Massimo; Finotti, Paola.

In: Oncotarget, Vol. 7, No. 45, 2016, p. 72923-72940.

Research output: Contribution to journalArticle

Tramentozzi, Elisa ; Ruli, Erlis ; Angriman, Imerio ; Bardini, Romeo ; Campora, Michela ; Guzzardo, Vincenza ; Zamarchi, Rita ; Rossi, Elisabetta ; Rugge, Massimo ; Finotti, Paola. / Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells. In: Oncotarget. 2016 ; Vol. 7, No. 45. pp. 72923-72940.
@article{a60d34bae2d64cba8a505ed5eaa105e3,
title = "Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells",
abstract = "Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature of Grp94 is its translocation from the ER to the cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both the tumor pathology and anti-tumor therapy. We wanted to address the question of whether Grp94 could be measured as liquid marker in cancer patients in order to make predictions of diagnostic and therapeutic relevance for the tumor. To this aim, we performed an in-depth investigation on patients with primary tumors of the gastrointestinal (GI) tract, using different methodological approaches to detect Grp94 in tumor tissues, plasma and peripheral blood mononuclear cells (PBMCs). Results indicate that Grp94 is not only the antigen highly expressed in any tumor tissue and in cells of tumor infiltrates, mostly B lymphocytes, but it is also found in the circulation. However, the only form in which Grp94 was detected in the plasma of any patients and in B lymphocytes induced to proliferate, was that of stable complexes with Immunoglobulin (Ig)G. Using a specific immune-enzyme assay to measure plasma Grp94-IgG complexes, we showed that Grp94-IgG complexes were significantly increased in cancer patients compared to healthy control subjects, serving as diagnostic tumor biomarker. Results also demonstrate that the stimulation of patient PBMCs with Grp94-IgG complexes led to an increased secretion of inflammatory cytokines that might drive a potentially beneficial anti-tumor effect.",
keywords = "Biomarkers, Gastrointestinal neoplasms, Heat shock Proteins, Immunoglobulins, Immunomodulation",
author = "Elisa Tramentozzi and Erlis Ruli and Imerio Angriman and Romeo Bardini and Michela Campora and Vincenza Guzzardo and Rita Zamarchi and Elisabetta Rossi and Massimo Rugge and Paola Finotti",
year = "2016",
doi = "10.18632/oncotarget.12141",
language = "English",
volume = "7",
pages = "72923--72940",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "45",

}

TY - JOUR

T1 - Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells

AU - Tramentozzi, Elisa

AU - Ruli, Erlis

AU - Angriman, Imerio

AU - Bardini, Romeo

AU - Campora, Michela

AU - Guzzardo, Vincenza

AU - Zamarchi, Rita

AU - Rossi, Elisabetta

AU - Rugge, Massimo

AU - Finotti, Paola

PY - 2016

Y1 - 2016

N2 - Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature of Grp94 is its translocation from the ER to the cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both the tumor pathology and anti-tumor therapy. We wanted to address the question of whether Grp94 could be measured as liquid marker in cancer patients in order to make predictions of diagnostic and therapeutic relevance for the tumor. To this aim, we performed an in-depth investigation on patients with primary tumors of the gastrointestinal (GI) tract, using different methodological approaches to detect Grp94 in tumor tissues, plasma and peripheral blood mononuclear cells (PBMCs). Results indicate that Grp94 is not only the antigen highly expressed in any tumor tissue and in cells of tumor infiltrates, mostly B lymphocytes, but it is also found in the circulation. However, the only form in which Grp94 was detected in the plasma of any patients and in B lymphocytes induced to proliferate, was that of stable complexes with Immunoglobulin (Ig)G. Using a specific immune-enzyme assay to measure plasma Grp94-IgG complexes, we showed that Grp94-IgG complexes were significantly increased in cancer patients compared to healthy control subjects, serving as diagnostic tumor biomarker. Results also demonstrate that the stimulation of patient PBMCs with Grp94-IgG complexes led to an increased secretion of inflammatory cytokines that might drive a potentially beneficial anti-tumor effect.

AB - Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature of Grp94 is its translocation from the ER to the cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both the tumor pathology and anti-tumor therapy. We wanted to address the question of whether Grp94 could be measured as liquid marker in cancer patients in order to make predictions of diagnostic and therapeutic relevance for the tumor. To this aim, we performed an in-depth investigation on patients with primary tumors of the gastrointestinal (GI) tract, using different methodological approaches to detect Grp94 in tumor tissues, plasma and peripheral blood mononuclear cells (PBMCs). Results indicate that Grp94 is not only the antigen highly expressed in any tumor tissue and in cells of tumor infiltrates, mostly B lymphocytes, but it is also found in the circulation. However, the only form in which Grp94 was detected in the plasma of any patients and in B lymphocytes induced to proliferate, was that of stable complexes with Immunoglobulin (Ig)G. Using a specific immune-enzyme assay to measure plasma Grp94-IgG complexes, we showed that Grp94-IgG complexes were significantly increased in cancer patients compared to healthy control subjects, serving as diagnostic tumor biomarker. Results also demonstrate that the stimulation of patient PBMCs with Grp94-IgG complexes led to an increased secretion of inflammatory cytokines that might drive a potentially beneficial anti-tumor effect.

KW - Biomarkers

KW - Gastrointestinal neoplasms

KW - Heat shock Proteins

KW - Immunoglobulins

KW - Immunomodulation

UR - http://www.scopus.com/inward/record.url?scp=84995777936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995777936&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.12141

DO - 10.18632/oncotarget.12141

M3 - Article

AN - SCOPUS:84995777936

VL - 7

SP - 72923

EP - 72940

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 45

ER -