Immunological microenvironment in prostate cancer: High mast cell densities are associated with favorable tumor characteristics and good prognosis

Fleischmann, Achim; Schlomm, Thorsten; Köllermann, Jens; Sekulić, Nikolina; Huland, Hartwig; Mirlacher, Martina; Sauter, Guido; Simon, Ronald; Erbersdobler, Andreas

doi:10.1002/pros.20948

Cited by 128 publications

(117 citation statements)

References 28 publications

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“…This could explain the contradictory findings regarding mast cell function in PC by other researchers [12][13] and are in line with the described plasticity of the role of mast cells in tumor biology. 8 -11 Mast cells produce a broad repertoire of cytokines to regulate inflammatory responses, growth factors to stimulate blood vessels and fibroblasts, and enzymes capable of releasing growth factors from extracellular matrix.…”

Section: Discussionsupporting

confidence: 78%

“…Similarly, in men, they relate to a poor prognosis and correlates with GS. In contrast, intratumoral mast cells correlate negatively with the presence of metastasis, tumor stage, GS, peritumoral blood vessel density, and tumor cell proliferation as well as relates to a good prognosis in PC, similar to results from a large cohort of breast 43 and prostate cancer 13 patients. The mechanism behind this is not evaluated in this study but could speculatively relate to their ability to regulate immunity.…”

Section: Discussionsupporting

confidence: 74%

“…High mast cell density in the nonmalignant part of the prostate was related to high GS (Table 2), but in contrast to the findings in the AT-1 model, it was not correlated with vascular density in this tissue compartment. In contrast, patients with a low number of mast cells in the tumor compartment had, as described previously in surgically treated patients, 13 significantly shorter cancerspecific survival than patients with high number of mast cells in the tumors (15-year P-EFS was 51 Ϯ 6% and 71 Ϯ 6% in the two groups; Figure 4D, right). Because mast cells were found primarily in the stroma and high GS tumors contain a relatively low fraction of stroma compared with tumor cells, we repeated the multivariate analysis including GS and local tumor stage.…”

Section: Mast Cells Are Related To Clinical Outcomesupporting

confidence: 59%

“…[12][13] In both nonmalignant and malignant human prostate tissue, mast cells were found principally in the stroma. In prostate tumors only a few mast cells were detected in the epithelial compartment ( Figure 4, A and B).…”

Section: Mast Cells Are Located In the Prostate Stroma In Menmentioning

confidence: 99%

See 3 more Smart Citations

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

Johansson

Rudolfsson

Hammarsten

et al. 2010

The American Journal of Pathology

190

187

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Mast cells affect growth in various humanCancer growth is dependent on the reciprocal interaction between tumor cells and their microenvironment. Cancerassociated fibroblasts, 1 vascular cells, and inflammatory cells such as macrophages [2][3][4] have been shown to promote prostate tumor growth. Mast cells are also of importance for tumor growth and have been shown to affect angiogenesis 5-7 but are also potent regulators of inflammation and thus their specific function during tumor progression is complex and shows significant plasticity. 8 -10 Their role in prostate cancer (PC) in patients was recently explored in two separate studies using tryptase and c-Kit as markers for mast cells. These studies lacked the discrepancy between intra-and peritumoral mast cells and did not identify mast cells as independent prognostic variables. One of the studies showed that tryptase-positive mast cells were related to poor outcome in PC patients. 12 The other study analyzed c-Kit-positive cells in tumor samples from PC patients and found an association between increased mast cell numbers and a favorable prognosis. 13Castration therapy is the gold standard for treatment of patients with metastatic PC, but in the majority of cases the formation of castrate-resistant prostate tumors is inevitable. The mechanisms behind the relapse are not fully understood but could be related to changes in the androgen receptor and the tumor stroma.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 74%

Section: Mast Cells Are Related To Clinical Outcomesupporting

confidence: 59%

Section: Mast Cells Are Located In the Prostate Stroma In Menmentioning

confidence: 99%

See 2 more Smart Citations

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

Johansson

Rudolfsson

Hammarsten

et al. 2010

The American Journal of Pathology

190

187

View full text Add to dashboard Cite

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“…This process, described as a reactive stroma, [5][6][7] is similar to the stroma reaction in wounds. 8 Reactive tumor stroma in prostate cancer is accompanied by changes in gene expression, 9 decreased androgen-receptor staining, 10 increased angiogenesis, 11 accumulation of inflammatory cells, [12][13][14] and alterations in the extracellular matrix, 5,15 and the magnitude of these changes are all related to outcome.…”

mentioning

confidence: 99%

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

Josefsson

Adamo

Hammarsten

et al. 2011

The American Journal of Pathology

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Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome. (Am J Pathol

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Label‐Free Homogeneous Immunosensor Based on FRET for the Detection of Virus Antibody in Serum

Zhang

Gao

Zhou

et al. 2012

Chemistry An Asian Journal

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Immunological microenvironment in prostate cancer: High mast cell densities are associated with favorable tumor characteristics and good prognosis

Cited by 128 publications

References 28 publications

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

Label‐Free Homogeneous Immunosensor Based on FRET for the Detection of Virus Antibody in Serum

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