Strategies to Suppress Tumor Angiogenesis and Metastasis, Overcome Multi-Drug Resistance in Cancer, Target Telomerase and Apoptosis Pathways

2021 ◽  
pp. 312-338
Author(s):  
Mohd Aleem ◽  
Deepti Sharma ◽  
Deepshikha Sharma ◽  
Siddhartha Dan ◽  
Pooja Gupta ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tumor Angiogenesis ◽  
Cell Cycle Control ◽  
Acquired Resistance ◽  
Multi Drug Resistance ◽  
Signal Transduction Pathways ◽  
Long Time ◽  
Apoptosis Pathways ◽  
Tumor Growth And Metastasis ◽  
Resistance To Chemotherapy

Cancer has been a worldwide topic in the medical field for a very long time. As angiogenesis is essential for tumor growth and metastasis, controlling tumor-associated angiogenesis is a promising tactic in limiting cancer progression. In cancer patients, multidrug resistance (MDR) is most widely used phenomenon by which cancer acquired resistance to chemotherapy. This resistance to chemotherapy occurs due to the formation of insulated tumor microenvironment which remains a major hurdle in the cure of various types of cancer. The mechanisms that cause malignant growth of cells include cell cycle control, signal transduction pathways, apoptosis, telomere stability, and interaction with the extracellular matrix. This chapter focuses on current strategies to suppress tumor angiogenesis for cancer therapy, various mechanisms involved in the development of MDR in cancer cells, which in turn will help us to identify possible strategies to overcome these MDR mechanisms and a variety of procedures that involves targeting apoptotic and telomerase pathways to suppress tumor progression.

scholarly journals LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
De Novo ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Clinical Samples ◽  
Autophagy Flux ◽  
Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

scholarly journals Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis

2014 ◽  
Vol 7 ◽  
pp. CGM.S14501 ◽  
Author(s):  
Patrick C. Hackler ◽  
Sarah Reuss ◽  
Raymond L. Konger ◽  
Jeffrey B. Travers ◽  
Ravi P. Sahu
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Lung Tumor ◽  
Platelet Activating Factor ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Melanoma Tumor ◽  
Tumor Growth And Metastasis ◽  
The Impact

Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.

scholarly journals Bidirectional Interaction Between Cancer Cells and Platelets Provides Potential Strategies for Cancer Therapies

2021 ◽  
Vol 11 ◽  
Author(s):  
Liuting Yu ◽  
Yao Guo ◽  
Zhiguang Chang ◽  
Dengyang Zhang ◽  
Shiqiang Zhang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Antiplatelet Agents ◽  
Cancer Therapies ◽  
Therapeutic Approaches ◽  
Tumor Cell Adhesion ◽  
Essential Components ◽  
Tumor Growth And Metastasis ◽  
Induced Apoptosis ◽  
Adhesion And Invasion

Platelets are essential components in the tumor microenvironment. For decades, clinical data have demonstrated that cancer patients have a high risk of thrombosis that is associated with adverse prognosis and decreased survival, indicating the involvement of platelets in cancer progression. Increasing evidence confirms that cancer cells are able to induce production and activation of platelets. Once activated, platelets serve as allies of cancer cells in tumor growth and metastasis. They can protect circulating tumor cells (CTCs) against the immune system and detachment-induced apoptosis while facilitating angiogenesis and tumor cell adhesion and invasion. Therefore, antiplatelet agents and platelet-based therapies should be developed for cancer treatment. Here, we discuss the mechanisms underlying the bidirectional cancer-platelet crosstalk and platelet-based therapeutic approaches.

The cholesterol metabolite 27-hydroxycholesterol increases the secretion of extracellular vesicles which promote breast cancer progression

Endocrinology ◽  
2021 ◽  
Author(s):  
Amy E Baek ◽  
Natalia Krawczynska ◽  
Anasuya Das Gupta ◽  
Svyatoslav Victorovich Dvoretskiy ◽  
Sixian You ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Myeloid Cells ◽  
Breast Cancer Progression ◽  
Label Free ◽  
Tumor Growth And Metastasis ◽  
Promote Breast Cancer

Abstract Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite, 27-hydroxycholesterol (27HC), as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an estrogen receptor (ER) modulator to promote the growth of ERα+ tumors, and a liver x receptor (LXR) ligand in myeloid immune cells to establish an immune-suppressive program. In fact, the metastatic properties of 27HC require the presence of myeloid cells, with neutrophils (PMNs) being essential for the increase in lung metastasis in murine models. In an effort to further elucidate the mechanisms by which 27HC alters breast cancer progression, we made the striking finding that 27HC promoted the secretion of extracellular vesicles (EVs), a diverse assortment of membrane bound particles that include exosomes. The resulting EVs had a size distribution that was skewed slightly larger, compared to EVs generated by treating cells with vehicle. The increase in EV secretion and size was consistent across three different subtypes: primary murine PMNs, RAW264.7 monocytic cells and 4T1 murine mammary cancer cells. Label-free analysis of 27HC-EVs indicated that they had a different metabolite composition to those from vehicle-treated cells. Importantly, 27HC-EVs from primary PMNs promoted tumor growth and metastasis in two different syngeneic models, demonstrating the potential role of 27HC induced EVs in the progression of breast cancer. EVs from PMNs were taken up by cancer cells, macrophages and PMNs, but not T cells. Since EVs did not alter proliferation of cancer cells, it is likely that their pro-tumor effects are mediated through interactions with myeloid cells. Interestingly, RNA-seq analysis of tumors from 27HC-EV treated mice do not display significantly altered transcriptomes, suggesting that the effects of 27HC-EVs occur early on in tumor establishment and growth. Future work will be required to elucidate the mechanisms by which 27HC increases EV secretion, and how these EVs promote breast cancer progression. Collectively however, our data indicate that EV secretion and content can be regulated by a cholesterol metabolite, which may have detrimental effects in terms of disease progression, important findings given the prevalence of both breast cancer and hypercholesterolemia.

scholarly journals Main Inflammatory Cells and Potentials of Anti-Inflammatory Agents in Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1153 ◽  
Author(s):  
Takuji Hayashi ◽  
Kazutoshi Fujita ◽  
Makoto Matsushita ◽  
Norio Nonomura
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Immune Cells ◽  
Acquired Resistance ◽  
Suppressor Cells ◽  
Basic Research ◽  
Inflammatory Cells ◽  
Intercellular Signaling ◽  
Prostate Cancer Progression ◽  
Anti Inflammatory

Prostate cancer is the most common type of cancer and the leading cause of cancer deaths among men in many countries. Preventing progression is a major concern for prostate cancer patients on active surveillance, patients with recurrence after radical therapies, and patients who acquired resistance to systemic therapies. Inflammation, which is induced by various factors such as infection, microbiome, obesity, and a high-fat diet, is the major etiology in the development of prostate cancer. Inflammatory cells play important roles in tumor progression. Various immune cells including tumor-associated neutrophils, tumor-infiltrating macrophages, myeloid-derived suppressor cells, and mast cells promote prostate cancer via various intercellular signaling. Further basic studies examining the relationship between the inflammatory process and prostate cancer progression are warranted. Interventions by medications and diets to control systemic and/or local inflammation might be effective therapies for prostate cancer progression. Epidemiological investigations and basic research using human immune cells or mouse models have revealed that non-steroidal anti-inflammatory drugs, metformin, statins, soy isoflavones, and other diets are potential interventions for preventing progression of prostate cancer by suppressing inflammation. It is essential to evaluate appropriate indications and doses of each drug and diet.

scholarly journals Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhe-Xiang Wang ◽  
Shao-Chun Ren ◽  
Zi-Song Chang ◽  
Jing Ren
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Clinical Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Expression Levels ◽  
Human Osteosarcoma ◽  
Promising Therapeutic Target ◽  
Tumor Growth And Metastasis

Background. Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still required to combat this disease. In recent years, the involvement of KIF2A in cancer progression has been widely revealed; however, its potential effect on osteosarcoma development remains unknown. This study is to assess the KIF2A expression levels in human osteosarcoma tissues and explore its potential role in osteosarcoma development. Methods. Immunohistochemical (IHC) assays were conducted to evaluate the expression levels of KIF2A in a total of 74 samples of osteosarcoma tissues and adjacent nontumor tissues. According to the staining intensity in tumor tissues, patients were divided into highly expressed and low expression KIF2A groups. The possible links between the KIF2A expression and the clinical pathological features were explored and analyzed, and the effects of KIF2A on osteosarcoma cell proliferation, migration, and invasion were detected through colony formation assay, MTT assay, wound closure assay, and transwell assay, respectively. The effects of KIF2A on tumor growth and metastasis were detected by the use of animal models. Results. KIF2A was highly expressed in human osteosarcoma tissues. Meanwhile, KIF2A was obviously correlated to the tumor size ( P = 0.001 ∗ ) and clinical stage ( P = 0.014 ∗ ) of osteosarcoma patients. Our results also revealed that the ablation of KIF2A dramatically blocked the proliferation, migration, and invasion capacity of osteosarcoma cells in vitro and blocked tumor growth and metastasis in mice. Conclusions. We investigated the involvement of KIF2A in the development and metastasis of osteosarcoma and therefore thought KIF2A as a promising therapeutic target for osteosarcoma treatment.

scholarly journals PCDHGB7 Increases Chemosensitivity to Carboplatin by Inhibiting HSPA9 via Inducing Apoptosis in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Siqi Hou ◽  
Ming Shan ◽  
Chunyang Gao ◽  
Xinxin Feng ◽  
Yongheng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Caspase 3 ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Underlying Mechanism ◽  
High Recurrence Rate ◽  
Tnbc Cell ◽  
Resistance To Chemotherapy

Breast cancer is one of the most serious cancers worldwide, and chemotherapy resistance frequently drives cancer progression. Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis given its resistance to chemotherapy. In our previous study, we found a remarkable abnormal methylation modification of the PCDHGB7 gene in breast cancer. However, the roles of PCDHGB7 in the progression and treatment of breast cancer are unclear. In this study, we examined the effects of PCDHGB7 on the sensitivity of TNBC cells to carboplatin and investigated the underlying mechanism. By knocking down and overexpressing PCDHGB7 in HS578T and BT549 cells, we confirmed that PCDHGB7 increases TNBC cell chemosensitivity to carboplatin. Mechanistically, we found that PCDHGB7 negatively regulates the expression of HSPA9, uplifting its inhibition on P53 translocation and caspase-3 activation. Thus, we demonstrated that PCDHGB7 increases chemosensitivity of TNBC cells to carboplatin by inhibiting HSPA9 via inducing apoptosis. PCDHGB7 and HSPA9 represent potential therapeutic targets for chemosensitivity in breast cancer.

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