TME Pathway-Related Proteins

The tumor microenvironment (TME) plays a key role in all aspects of cancer, including tumorigenesis, progression, invasion, metastasis, and drug resistance. To fully understand TME, it is necessary to scrutinize signaling pathways that are responsible for its characteristics. These pathways, such as integrin, TGF-β, Hedgehog, Notch, and Wnt, are highly conserved throughout evolution and have a major impact on cell fate. These pathways have been reported to be upregulated in TME, suggesting that they have the potential to be important targets for intervention and regulation in the TME.

Fig. 1 Cross-regulation of TME pathways. (Malla R R, et al., 2022)

Alfa Cytology provides various target proteins related to the TME pathway, providing valuable tools for cancer treatment and accelerating your research and development process.

Targets of Integrin Signaling Pathways

Integrin signaling plays a crucial role in connecting with other receptor tyrosine kinase (RTK) pathways and facilitating downstream signal transduction through MAPK/Erk, PI3-Akt, JNK, and SAPK pathways. In the context of TME, Integrin is involved in various processes such as promoting the binding of tumor cells to the extracellular matrix (ECM), facilitating angiogenesis, and playing a significant role in cancer cell metastasis and aggressiveness. As a result, scientists are actively investigating Integrins as potential targets for anticancer therapy, utilizing integrin blockers. For example, a promising candidate currently undergoing clinical trials is an Arg-Gly-Asp (RGD) pentapeptide that specifically targets the avb3 and avb5 integrins.

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Targets of TGF-Β Signaling Pathways

Transforming growth factor β (TGF-β) is a multifunctional cytokine for immune homeostasis and immune tolerance, playing a key role in TME and a dual role in carcinogenesis. In early-stage tumors, the TGF-β pathway induces apoptosis and inhibits tumor cell proliferation. However, in advanced stages, it has a tumor-promoting role by regulating genomic instability, epithelial-mesenchymal transition (EMT), neoangiogenesis, immune evasion, cell motility, and metastasis. Increased secretion of TGF-β in the TME can affect the growth of cancer cells and promote migration, invasion, and angiogenesis. Data from preclinical or clinical trials suggest that blocking TGF-β signaling is an effective approach to treating tumors.

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Targets of Notch Signaling Pathways

The Notch signaling pathway is a contact-dependent signaling pathway that plays a crucial role in cell fate decisions between neighboring cells and is involved in various aspects of the TME and the interactions within it. The Notch pathway mainly consists of four parts: Notch receptor, Notch ligand, CSLDNA binding protein, and downstream target genes.

Different TME components widely express Notch receptors and ligands. Notch signaling has been found to participate in fibroblast activation, angiogenesis, and the maintenance of the cancer stem cell niche. It also influences the composition of the immune infiltrate at the tumor site and can be regulated by physical and chemical heterogeneity within the TME. Understanding the role of Notch signaling in these processes is important for unraveling the intricate dynamics of the TME and exploring potential therapeutic interventions.

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Targets of VEGF Signaling Pathways

Vascular endothelial growth factor (VEGF) influences the proliferation and migration of endothelial cells in the TME, as well as the secretion of growth factors and the activation of downstream signaling molecules that result in the formation of new blood vessels. In addition, VEGF also promotes vascular permeability, making the TME more susceptible to the accumulation of growth factors, cytokines, and metabolic waste products, which affects tumor spread and therapeutic efficacy.

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Targets of Other Important Signaling Pathways

There are also many signaling pathways associated with the TME and play important roles in tumorigenesis and development. For example, in non-tumor cells within the TME, active EGFR signaling is thought to play a supportive role in tumor cell proliferation, angiogenesis, and metastasis. Hepatocyte growth factor (HGF), a cytokine produced by mesenchymal fibroblasts, plays an important role in tumor development by its activity against cancer cells. Fibroblast growth factor (FGF) signaling has different effects on target cells including various biological processes such as proliferation, anti-apoptosis, stemness, epithelial-mesenchymal transition (EMT), drug resistance, angiogenesis, and invasion. The Wnt signaling pathway is an important regulator of embryonic development, tissue homeostasis, wound repair, stemness control, and malignancy. Dysregulation of its signaling has been associated with the onset, development, and metastasis of different types of human cancers. The hedgehog (HH) pathway plays an important role in embryonic development as well as adult tissue regeneration and maintenance. Overactive HH signaling leads to basal cell carcinoma as well as lung, prostate, pancreatic, breast, and ovarian cancers.

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As a prominent player in the field of TME research, Alfa Cytology is committed to providing researchers with high-quality tools and reagents. These products are designed to facilitate the target identification related to TME pathways and accelerate the development of novel therapeutics.

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Reference

1. Malla R R, Kiran P. Tumor microenvironment pathways: Cross regulation in breast cancer metastasis. Genes & diseases. 2022, 9(2): 310-324.