Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumor cells and tumor-associated macrophages: secreted proteins as potential targets for therapy.

ABSTRACT: Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

SUBMITTER: Baay M

PROVIDER: S-EPMC3227419 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Tumor cells and tumor-associated macrophages: secreted proteins as potential targets for therapy.

Baay Marc M Brouwer Anja A Pauwels Patrick P Peeters Marc M Lardon Filip F

Clinical & developmental immunology 20111117

Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provid ...[more]

PMID: 22162712

Similar Datasets

Tumor-associated macrophages, potential targets for cancer treatment.

Project description:The fact that various immune cells, including macrophages, can be found in tumor tissues has long been known. With the introduction of concept that macrophages differentiate into a classically or alternatively activated phenotype, the role of tumor-associated macrophages (TAMs) is now beginning to be elucidated. TAMs act as "protumoral macrophages", contributing to disease progression. As the relationship between TAMs and malignant tumors becomes clearer, TAMs are beginning to be seen as potential therapeutic targets in these cases. In this review, we will discuss how TAMs can be used as therapeutic targets of cancer in clinics.

| S-EPMC5549387 | biostudies-literature

Tumor-Associated Macrophages: A Potential Target for Cancer Therapy.

Project description:Macrophages, an important class of innate immune cells that maintain body homeostasis and ward off foreign pathogens, exhibit a high degree of plasticity and play a supportive role in different tissues and organs. Thus, dysfunction of macrophages may contribute to advancement of several diseases, including cancer. Macrophages within the tumor microenvironment are known as tumor-associated macrophages (TAMs), which typically promote cancer cell initiation and proliferation, accelerate angiogenesis, and tame anti-tumor immunity to promote tumor progression and metastasis. Massive infiltration of TAMs or enrichment of TAM-related markers usually indicates cancer progression and a poor prognosis, and consequently tumor immunotherapies targeting TAMs have gained significant attention. Here, we review the interaction between TAMs and cancer cells, discuss the origin, differentiation and phenotype of TAMs, and highlight the role of TAMs in pro-cancer functions such as tumor initiation and development, invasive metastasis, and immunosuppression. Finally, we review therapies targeting TAMs, which are very promising therapeutic strategies for malignant tumors.

| S-EPMC8222665 | biostudies-literature

Bipolar Tumor-Associated Macrophages in Ovarian Cancer as Targets for Therapy.

Project description:Ovarian cancer, a rare but fatal disease, has been a challenging area in the field of gynecological cancer. Ovarian cancer is characterized by peritoneal metastasis, which is facilitated by a cross-talk between tumor cells and other cells in the tumor microenvironment (TME). In epithelial ovarian cancer, tumor-associated macrophages (TAMs) constitute over 50% of cells in the peritoneal TME and malignant ascites, and are potential targets for therapy. Here, we review the bipolar nature of TAMs and the evolving strategies to target TAMs in ovarian cancer.

| S-EPMC6210537 | biostudies-literature

Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy.

Project description:In triple-negative breast cancer (TNBC), the lack of therapeutic markers and effective targeted therapies result in an incurable metastatic disease associated with a poor prognosis. Crosstalks within the tumor microenvironment (TME), including those between cancer and stromal cells, affect the tumor heterogeneity, growth, and metastasis. Previously, we have demonstrated that IL-6, IL-8, and CCL5 play a significant role in TNBC growth and metastasis. In this study, we performed a systematic analysis of cytokine factors secreted from four stromal components (fibroblasts, macrophages, lymphatic endothelial cells, and blood microvascular endothelial cells) induced by four TNBC cell types. Through bioinformatic analysis, we selected putative candidates of secreted factors from stromal cells, which are involved in EMT activity, cell proliferation, metabolism, and matrisome pathways. Among the candidates, LCN2, GM-CSF, CST3, IL-6, IL-8, and CHI3L1 are ranked highly. Significantly, Lipocalin-2 (LCN2) is upregulated in the crosstalk of stromal cells and four different TNBC cells. We validated the increase of LCN2 secreted from four stromal cells induced by TNBC cells. Using a specific LCN2 antibody, we observed the inhibition of TNBC cell growth and migration. Taken together, these results propose secreted factors as molecular targets to treat TNBC progression via crosstalk with stromal components.

| S-EPMC7515526 | biostudies-literature

New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy.

Project description:The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs), which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies.

| S-EPMC5128713 | biostudies-other

Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy.

Project description:Macrophages within solid tumors and metastatic sites are heterogenous populations with different developmental origins and substantially contribute to tumor progression. A number of tumor-promoting phenotypes associated with both tumor- and metastasis-associated macrophages are similar to innate programs of embryonic-derived tissue-resident macrophages. In contrast to recruited macrophages originating from marrow precursors, tissue-resident macrophages are seeded before birth and function to coordinate tissue remodeling and maintain tissue integrity and homeostasis. Both recruited and tissue-resident macrophage populations contribute to tumor growth and metastasis and are important mediators of resistance to chemotherapy, radiation therapy, and immune checkpoint blockade. Thus, targeting various macrophage populations and their tumor-promoting phenotypes holds therapeutic promise. Here, we discuss various macrophage populations as regulators of tumor progression, immunity, and immunotherapy. We provide an overview of macrophage targeting strategies, including therapeutics designed to induce macrophage depletion, impair recruitment, and induce repolarization. We also provide a perspective on the therapeutic potential for macrophage-specific acquisition of trained immunity as an anti-cancer agent and discuss the therapeutic potential of exploiting macrophages and their traits to reduce tumor burden.

| S-EPMC8074766 | biostudies-literature

Tumor-Associated Macrophages Induce Endocrine Therapy Resistance in ER+ Breast Cancer Cells.

Project description:Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models. Proliferation, migration, and colony formation assays were performed to evaluate tamoxifen and ICI 182,780 resistance and confirmed in a mouse-xenograft model. Molecular mechanisms were investigated using cytokine antibody arrays, WB, ELISA, ChIP, siRNA, and qPCR-assays. In our simulated pro-inflammatory tumor microenvironment, tumor-associated macrophages promoted proliferation, migration, invasiveness, and breast tumor growth of ER+ cells, rendering these estrogen-dependent breast cancer cells resistant to estrogen withdrawal and tamoxifen or ICI 182,780 treatment. Crosstalk between breast cancer cells and conditioned macrophages induced sustained release of pro-inflammatory cytokines from both cell types, activation of NF-κB/STAT3/ERK in the cancer cells and hyperphosphorylation of ERα, which resulted constitutively active. Our simulated tumor microenvironment strongly altered endocrine and inflammatory signaling pathways in breast cancer cells, leading to endocrine resistance in these cells.

| S-EPMC6406935 | biostudies-literature

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy.

Project description:Tumor microenvironment (TME) is composed of tumor cells and surrounding non-tumor stromal cells, mainly including tumor associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts (CAFs). The TAMs are the major components of non-tumor stromal cells, and play an important role in promoting the occurrence and development of tumors. Macrophages originate from bone marrow hematopoietic stem cells and embryonic yolk sacs. There is close crosstalk between TAMs and tumor cells. With the occurrence of tumors, tumor cells secrete various chemokines to recruit monocytes to infiltrate tumor tissues and further promote their M2-type polarization. Importantly, M2-like TAMs can in turn accelerate tumor growth, promote tumor cell invasion and metastasis, and inhibit immune killing to promote tumor progression. Therefore, targeting TAMs in tumor tissues has become one of the principal strategies in current tumor immunotherapy. Current treatment strategies focus on reducing macrophage infiltration in tumor tissues and reprogramming TAMs to M1-like to kill tumors. Although these treatments have had some success, their effects are still limited. This paper mainly summarized the recruitment and polarization of macrophages by tumors, the support of TAMs for the growth of tumors, and the research progress of TAMs targeting tumors, to provide new treatment strategies for tumor immunotherapy.

| S-EPMC7670061 | biostudies-literature

Tumor-Associated Macrophages as Target for Antitumor Therapy.

Project description:It is well known that the microenvironment of solid tumors is rich in inflammatory cells that influence tumor growth and development. Macrophages, called tumor-associated macrophages (TAMs), are the most abundant immune cell population present in tumor tissue. Several studies have demonstrated that the density of TAMs is associated with a poor prognosis and positively correlates with tumor growth. Several studies have proved that TAMs may activate and protect tumor stem cells, stimulate their proliferation as well as promote angiogenesis and metastasis. Furthermore, TAMs-derived cytokines and other proteins, such as CCL-17, CCL-22, TGF-?, IL-10, arginase 1, and galectin-3, make a significant contribution to immunosuppression. Since TAMs influence various aspects of cancer progression, there are many attempts to use them as a target for immunotherapy. The numerous studies have shown that the primary tumor growth and the number of metastatic sites can be significantly decreased by decreasing the population of macrophages in tumor tissue, for example, by blocking recruitment of monocytes or eliminating TAMs already present in the tumor tissue. Moreover, there are attempts at reprogramming TAMs into proinflammatory M1 macrophages or neutralizing the protumoral products of TAMs. Another approach uses TAMs for anticancer drug delivery into the tumor environment. In this review, we would like to summarize the clinical and preclinical trials that were focused on macrophages as a target for anticancer therapies.

| S-EPMC5851686 | biostudies-literature

HSPA12B Secreted by Tumor-Associated Endothelial Cells Might Induce M2 Polarization of Macrophages via Activating PI3K/Akt/mTOR Signaling.

Project description:Purpose:The intratumoral microenvironment of head and neck squamous cell carcinoma (HNSC) is highly immunosuppressive. In this study, we explored the potential functional role of HSPA12B secreted by tumor-associated endothelial cells (TECs) in M2 polarization of macrophages. Materials and Methods:Bulk-seq data from TCGA-HNSC and single-cell RNA-seq data from GSE103322 (with over 5000 cells from 18 primary HNSC cases) were used for bioinformatic analysis. RAW264.7 cell line was used for in vitro studies. Results:TECs in HNSC had significantly higher expression and secretion of HSPA12B, compared to normal human umbilical vein endothelial cells (HUVECs). Exogenous HSPA12B treatment increased the expression of M2 macrophage marker CD163 and CD206 on RAW264.7 cells in a dose-dependent manner but had no significant influence on CD86, an M1 macrophage marker. OLR1, a known receptor of HSP70 proteins, was specifically expressed in tumor-associated macrophages (TAMs) in HNSC. OLR1 knockdown significantly impaired HSPA12B uptake by RAW264.7 cells and weakened HSPA12B-induced CD163 and CD206 upregulation. HSPA12B treatment increased the expression of p-PI3K, p-Akt and p-mTOR in a dose-dependent manner in RAW264.7 cells. OLR1 inhibition and LY294002 treatment significantly weakened the effects HSPA12B on activating the PI3K/Akt/mTOR signaling and M2 marker expression. Conclusion:Based on these findings, we speculated that aberrantly expressed and secreted HSPA12B by TECs could be taken by macrophages partly via OLR1, leading to subsequent activation of the PI3K/Akt/mTOR signaling pathway and elevated expression of M2 markers. This mechanism shows a novel cross-talk between TECs and TAMs, which contributes to the intratumoral immunosuppressive microenvironment.

| S-EPMC7494226 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data