Cellular Interactions in the Tumor Microenvironment: The Role of Secretome

Cunha, Bianca Rodrigues da; Domingos, Célia; Stefanini, Ana Carolina Buzzo; Henrique, Tiago; Polachini, Giovana Mussi; Castelo‐Branco, Pedro; Tajara, Eloíza H.

doi:10.7150/jca.21780

Cited by 101 publications

(90 citation statements)

References 156 publications

(193 reference statements)

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“…Active and dynamic cross-talk between these components of the tumor microenvironment and the neoplastic cells is crucial in providing signals that enhance cancer cell growth and survival, as well as the metastatic property of tumor cells [3]. The tumor-stroma interaction can occur both directly, via cell-cell interaction/communication, and through the action of a bunch of molecules secreted by both neoplastic cells and cancer-associated immune/nonimmune cells [4]. Identification of such molecules has largely advanced our understanding of the mechanisms promoting cancer initiation and progression and facilitated the development of drugs useful to combat cancer.…”

Section: Introductionmentioning

confidence: 99%

Role of Interleukin-34 in Cancer

Franzè

Stolfi

Troncone

et al. 2020

Cancers

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Cross-talk between cancer cells and the immune cells occurring in the tumor microenvironment is crucial in promoting signals that foster tumor growth and metastasis. Both cancer cells and immune cells secrete various interleukins (IL), which, either directly or indirectly, stimulate cancer-cell proliferation, survival, and diffusion, as well as contribute to sculpt the immune microenvironment, thereby amplifying tumorigenic stimuli. IL-34, a cytokine produced by a wide range of cells, has been initially involved in the control of differentiation, proliferation, and survival of myeloid cells. More recent studies documented the overexpression of IL-34 in several cancers, such as hepatocarcinoma, osteosarcoma, multiple myeloma, colon cancer, and lung cancer, and showed that tumor cells can produce and functionally respond to this cytokine. In this review, we summarize the multiple roles of IL-34 in various cancers, with the aim to better understand the relationship between the expression of this cytokine and cancer behavior and to provide new insights for exploring a new potential therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Role of Interleukin-34 in Cancer

Franzè

Stolfi

Troncone

et al. 2020

Cancers

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“…Tumor microenvironment encompasses a complex mixture of cancer and non-cancerous cells (i.e., immune and endothelial cells, fibroblasts, adipocytes) and the extracellular matrix (ECM) [ 1 , 2 , 3 ]. A binary intertwined connection exists between all the components of tumor microenvironment as demonstrated in breast cancer (BC) [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…A binary intertwined connection exists between all the components of tumor microenvironment as demonstrated in breast cancer (BC) [ 2 , 3 ]. On one side, tumor cells directly interact each other and sculpt the ECM by releasing a variety of proteins that act as autocrine or paracrine factors influencing cancer and non-cancer cell proliferation, differentiation, and survival [ 1 ]. On the other hand, released factors from cancer-associated fibroblasts (CAF) and adipocytes (CAA) contribute to the tumorigenic phenotype of pre-malignant and malignant epithelial cells [ 4 ] promoting tumor cell proliferation, invasiveness, and growth.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the direct role of BC-associated fibroblasts in reducing hormone sensitivity and increasing resistance to endocrine therapy (i.e., Tamoxifen) has been demonstrated in ERα+ breast cancer cells [ 2 , 6 ]. The effect of heterotypic interaction between epithelial breast cancer cells and non-cancerous stromal cells have attracted major research interests focused in the discovery of new druggable pathways involved in cancer cell adaptation/resistance to stressful conditions and therapeutic strategies [ 1 , 2 , 4 ]. However, the identification of molecular factors and mechanisms by which cancer cells may affect the extracellular milieu and, in turn, neighbor normal and/or cancer epithelial cells in homotypic way is still in its infancy.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular Neuroglobin as a Stress-Induced Factor Activating Pre-Adaptation Mechanisms against Oxidative Stress and Chemotherapy-Induced Cell Death in Breast Cancer

Fiocchetti

Fernandez

Segatto

et al. 2020

Cancers

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Components of tumor microenvironment, including tumor and/or stromal cells-derived factors, exert a critical role in breast cancer (BC) progression. Here we evaluated the possible role of neuroglobin (NGB), a monomeric globin that acts as a compensatory protein against oxidative and apoptotic processes, as part of BC microenvironment. The extracellular NGB levels were evaluated by immunofluorescence of BC tissue sections and by Western blot of the culture media of BC cell lines. Moreover, reactive oxygen species (ROS) generation, cell apoptosis, and cell migration were evaluated in different BC cells and non-tumorigenic epithelial mammary cells treated with BC cells (i.e., Michigan Cancer Foundation-7, MCF-7) conditioned culture media and extracellular NGB. Results demonstrate that NGB is a component of BC microenvironment. NGB is released in tumor microenvironment by BC cells only under oxidative stress conditions where it can act as autocrine/paracrine factor able to communicate cell resilience against oxidative stress and chemotherapeutic treatment.

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“…For instance, breast cancer cells induce fibroblasts to secrete the ECM protein degrader ADAMTS1 through epigenetic changes 37 , demonstrating that the epigenetic reprogramming in stromal cells can be induced by cancer cells. The cancer secretome plays a vital role in the pro-tumorigenic effects of the TME, recruiting stromal cells and reprogramming them to support tumour progression [38][39][40] .…”

Section: Introductionmentioning

confidence: 99%

Embryonic Protein NODAL Regulates the Breast Tumour Microenvironment by Reprogramming Cancer-Derived Secretomes

Dieters-Castator

Dantonio

Piaseczny

et al. 2020

Preprint

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AbstractThe tumour microenvironment (TME) is an important mediator of breast cancer progression. Cancer-associated fibroblasts (CAFs) constitute a major component of the TME and may originate from tissue-associated fibroblasts or infiltrating mesenchymal stromal cells (MSCs). The mechanisms by which cancer cells activate fibroblasts and recruit MSCs to the TME are largely unknown, but likely include deposition of a pro-tumourigenic secretome. The secreted embryonic protein NODAL is clinically associated with breast cancer stage and promotes tumour growth, metastasis, and vascularization. Herein, we show that NODAL expression correlates with the presence of activated fibroblasts in human triple negative breast cancers and that it directly induces CAF phenotypes. We further show that NODAL reprograms cancer cell secretomes by simultaneously altering levels of chemokines (e.g. CXCL1), cytokines (e.g. IL-6) and growth factors (e.g. PDGFRA), leading to alterations in MSC chemotaxis. We therefore demonstrate a hitherto unappreciated mechanism underlying the dynamic regulation of the TME.

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Cellular Interactions in the Tumor Microenvironment: The Role of Secretome

Cited by 101 publications

References 156 publications

Role of Interleukin-34 in Cancer

Role of Interleukin-34 in Cancer

Extracellular Neuroglobin as a Stress-Induced Factor Activating Pre-Adaptation Mechanisms against Oxidative Stress and Chemotherapy-Induced Cell Death in Breast Cancer

Embryonic Protein NODAL Regulates the Breast Tumour Microenvironment by Reprogramming Cancer-Derived Secretomes

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