32
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mast cells are unique tissue-resident immune cells that secrete a diverse array of biologically active compounds that can stimulate, modulate, or suppress the immune response. Although mounting evidence supports that mast cells are consistently infiltrating tumors, their role as either a driving or an opposite force for cancer progression is still controversial. Particularly, in breast cancer, their function is still under discussion. While some studies have shown a protective role, recent evidence indicates that mast cells enhance blood and lymphatic vessel formation. Interestingly, one of the most important components of the mast cell cargo, the serine protease tryptase, is a potent angiogenic factor, and elevated serum tryptase levels correlate with bad prognosis in breast cancer patients. Likewise, histamine is known to induce tumor cell proliferation and tumor growth. In agreement, mast cell depletion reduces the size of mammary tumors and metastasis in murine models that spontaneously develop breast cancer. In this review, we will discuss the evidence supporting protumoral and antitumoral roles of mast cells, emphasizing recent findings placing mast cells as important drivers of tumor progression, as well as the potential use of these cells or their mediators as therapeutic targets.

          Related collections

          Most cited references103

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Mast Cell Function

          Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tumor associated macrophages and neutrophils in tumor progression.

            Tumor-associated macrophages (TAMs) are a key component of the tumor microenvironment and orchestrate various aspects of cancer. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to distinct signals macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a spectrum of activation states. Metabolic adaptation is a key component of macrophage plasticity and polarization, instrumental to their function in homeostasis, immunity and inflammation. Generally, TAMs acquire an M2-like phenotype that plays important roles in many aspects of tumor growth and progression. There is now evidence that also neutrophils can be driven towards distinct phenotypes in response to microenvironmental signals. The identification of mechanisms and molecules associated with macrophage and neutrophil plasticity and polarized activation provides a basis for new diagnostic and therapeutic strategies. Copyright © 2012 Wiley Periodicals, Inc.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Are Mast Cells MASTers in Cancer?

              Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin’s lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.
                Bookmark

                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2018
                5 February 2018
                : 2018
                : 2584243
                Affiliations
                1Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Doctores, Cuauhtémoc, 06720 Ciudad de Mexico, Mexico
                2Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
                3Programa de Servicio Social en Investigación en Salud, Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080 Ciudad de Mexico, Mexico
                4Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida Cuauhtémoc 330, Doctores, Cuauhtémoc, 06720 Ciudad de Mexico, Mexico
                Author notes

                Academic Editor: Shi Jin

                Author information
                http://orcid.org/0000-0003-2872-0459
                http://orcid.org/0000-0002-9547-2515
                Article
                10.1155/2018/2584243
                5832101
                29651440
                e17235cb-b9f0-4f30-8fa5-60abe3001b03
                Copyright © 2018 Angélica Aponte-López et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 August 2017
                : 8 November 2017
                : 26 November 2017
                Funding
                Funded by: Consejo Nacional de Ciencia y Tecnología
                Award ID: 223678
                Award ID: 482586/284102
                Categories
                Review Article

                Comments

                Comment on this article