ABSTRACT
The carcinogenesis and progression of cancer not only depend on the feature of tumor cell themselves, but also rely on the tumor microenvironment (TME). Numerous studies have shown that TME plays a crucial role in tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are important stromal cells in TME containing multiple functions, such as remodeling the extracellular matrix, regulating angiogenesis, interacting with adjacent tumor cells, and releasing a variety of molecules (such as cytokines, growth factors and exosomes) to regulate cell proliferation, invasion and metastasis. CAFs exhibit heterogeneity of origin and phenotype, and play dual roles in tumor progression. Recent studies have shown that CAFs are also involved in chemoresistance, suggesting that CAFs themselves and their downstream molecules and signal pathways could be the potential therapeutic target for cancer treatment. In this review, we summarized the role of CAFs in chemoresistance and underlying mechanism, and discussed the potential of targeting CAFs in overcoming drug resistance. However, the exploration of strategy for targeting CAFs is still at an early stage and requires further in-depth research.
ABSTRACT
To study the correlation between obesity and breast cancer incidence and progression in postmenopausal female, and provide theoretical instruction for breast cancer prevention and treatment, through being based on literature retrieval platforms such as Pubmed and CNKI, integrating multiple domestic and foreign related documents and various studies, it is found that obesity is one of the most important risk factors for breast cancer incidence and progression in postmenopausal women. On one hand, elevated postmenopausal estrogen levels in obese people directly promote the tumor behavior of breast cancer cells; on the other hand, adipose tissue privides a convenient immune environment for tumor growth by releasing inflammatory mediators, which indirectly promotes tumor development. In addition, obesity also induces the differentiation of adipose stem cell (ASCs) into cancer-associated fibroblasts (CAFs) and enhances the proliferation and invasive potential of breast cancer cells. As mentioned above, obesity increases the risk of breast cancer tumorigenesis and metastasis in postmenopausal women, and increases the risk of cancer-related death in breast cancer patients. The review elaborates the correlation between obesity and breast cancer incidence and progression in postmenopausal women, to provide new ideas for the prevention and treatment of breast cancer, which has essential clinical research value.
ABSTRACT
As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.
ABSTRACT
Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.
ABSTRACT
Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes. These molecules facilitate cell-extracellular matrix and cell-cell interactions, and they have been implicated in fibrosis, inflammation, thrombosis, and tumor metastasis. The role of integrins in tumor progression makes them promising targets for cancer treatment, and certain integrin antagonists, such as antibodies and synthetic peptides, have been effectively utilized in the clinic for cancer therapy. Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.
ABSTRACT
Cancer-associated fibroblasts(CAFs) are important cellular components of the tumor microenvironment. They have a variety of cellular sources, including resident fibroblasts, bone marrow mesenchymal stem cells and epithelial cells, which contribute to the development of tumors. CAFs play important roles in cancer initiation, progression, and metastasis,which can promote tumor proliferation and migration, promote tumor angiogenesis, regulate tumor immunity, and improve tumor drug resistance. Therefore, it is a promising development direction in tumor-targeted therapy. CAFs regulate the biological characteristics of tumor cells and other stromal cells through cell-to-cell contact, releases many regulatory factors and synthesizes and reshapes the extracellular matrix, and influences the occurrence and development of cancer in these ways. However, there are still many unresolved issues on the way in targeting CAFs for tumor therapy. For example, the origin and functional heterogeneity of CAFs still need to be further explored. This review mainly focuses on the summary of origin of CAFs, their roles in tumor development and the potential application in cancer targeted therapy, which will help to deepen the understanding of the roles of CAFs in cancer development and future cancer treatment.
ABSTRACT
@#[Abstract] Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components in tumor microenvironment, which not only provide physical support for tumor cells, but also play a key role in promoting or delaying tumor occurrence and development. CAFs are a highly abundant and heterogeneous mesenchymal cell line, which contain a large number of cell subsets with different phenotypes and functions. Targeted therapies for CAFs also emerge as demanded. In order to improve the understanding of CAFs in malignant tumors, we elucidate the heterogeneity of CAFs origins, phenotypes and related functions, as well as the research progress of their application in targeted therapy.
ABSTRACT
Cancer-associated fibroblasts (CAFs) are a major population that resides in the tumor microenvironment. Multiple soluble molecules secreted by CAFs remodel the extracellular matrix, thus promoting tumor growth, invasion and metastasis. It is now considered that CAFs play an important role in the regulation of tumor immunity, in which an increasing number of molecular mechanisms of tumor microenvironment remodeling are being discovered. This article reviews the molecular markers of CAFs, the crosstalk between CAFs and tumor cells or immune cells, as well as the progress on therapeutic targeting of CAFs.
ABSTRACT
Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been significantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs (predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment (such as extracellular matrix structure, growth factors, chemokines, matrix metalloproteinases) plays a significant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.