Abstract PO021: Carcinoma-associated mesenchymal stem/stromal cells enhance ovarian cancer metastasis and increase cancer cell clonal heterogeneity through direct mitochondrial transfer

2021 ◽  
Author(s):  
Catherine A. Pressimone ◽  
Leonard G. Frisbie ◽  
Alexander Pearson ◽  
Lan G. Coffman
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Clonal Heterogeneity ◽  
Mitochondrial Transfer

Cancer-associated fibroblasts (CAFs) in thyroid papillary carcinoma: molecular networks and interactions

2021 ◽  
pp. jclinpath-2020-207357
Author(s):  
Jeehoon Ham ◽  
Bin Wang ◽  
Joseph William Po ◽  
Amandeep Singh ◽  
Navin Niles ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Molecular Networks ◽  
Cancer Cell Growth ◽  
Molecular Events

In 1989, Stephen Paget proposed the ‘seed and soil’ theory of cancer metastasis. This theory has led to previous researchers focusing on the role of a tumour as a cancer seed and antiangiogenesis agents as cancer soil fumigant; for the latter to be effective, it is important for them to be able to distinguish cancer cells from stromal cells. However, antiangiogenesis agents have not produced dramatic survival benefits in vivo. This may be related to their inability to destroy the supporting stroma that promote cancer cell growth. Therefore, in order to effectively arrest cancer cell growth for therapeutic purposes, a paradigm shift is required in our fundamental approach to decipher the molecular events and networks in the stromal environment that cancer cells can thrive and proliferate. The pathogenesis of cancer is a multidimensional process of pathological molecular and cellular pathways, influencing different stromal properties and achieving a mutually negotiated crosstalk between cancer cells and stromal cells. This review summarises the clinical presentation of current knowledge of classical papillary thyroid carcinoma (PTC), emerging molecular diagnostics and future directions of classical PTC research.

scholarly journals Hexokinase 2 Regulates Ovarian Cancer Cell Migration, Invasion and Stemness via FAK/ERK1/2/MMP9/NANOG/SOX9 Signaling Cascades

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 813 ◽  
Author(s):  
Michelle K. Y. Siu ◽  
Yu-Xin Jiang ◽  
Jing-Jing Wang ◽  
Thomas H. Y. Leung ◽  
Chae Young Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Ovarian Cancer Cell ◽  
Lactate Production ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Hexokinase 2 ◽  
Cell Migration And Invasion

Metabolic reprogramming is a common phenomenon in cancers. Thus, glycolytic enzymes could be exploited to selectively target cancer cells in cancer therapy. Hexokinase 2 (HK2) converts glucose to glucose-6-phosphate, the first committed step in glucose metabolism. Here, we demonstrated that HK2 was overexpressed in ovarian cancer and displayed significantly higher expression in ascites and metastatic foci. HK2 expression was significantly associated with advanced stage and high-grade cancers, and was an independent prognostic factor. Functionally, knockdown of HK2 in ovarian cancer cell lines and ascites-derived tumor cells hindered lactate production, cell migration and invasion, and cell stemness properties, along with reduced FAK/ERK1/2 activation and metastasis- and stemness-related genes. 2-DG, a glycolysis inhibitor, retarded cell migration and invasion and reduced stemness properties. Inversely, overexpression of HK2 promoted cell migration and invasion through the FAK/ERK1/2/MMP9 pathway, and enhanced stemness properties via the FAK/ERK1/2/NANOG/SOX9 cascade. HK2 abrogation impeded in vivo tumor growth and dissemination. Notably, ovarian cancer-associated fibroblast-derived IL-6 contributed to its up-regulation. In conclusion, HK2, which is regulated by the tumor microenvironment, controls lactate production and contributes to ovarian cancer metastasis and stemness regulation via FAK/ERK1/2 signaling pathway-mediated MMP9/NANOG/SOX9 expression. HK2 could be a potential prognostic marker and therapeutic target for ovarian cancer.

scholarly journals Mesenchymal stem cells and their mitochondrial transfer: a double-edged sword

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng Li ◽  
Marco K.H. Cheung ◽  
Shuo Han ◽  
Zhao Zhang ◽  
Ling Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Cancer Metastasis ◽  
Cell Injury ◽  
Tissue Degeneration ◽  
Cell Based Therapy ◽  
Mitochondrial Transfer

Abstract Mitochondrial dysfunction has been linked to many diseases including organ degeneration and cancer. Mesenchymal stem cells/stromal cells (MSCs) provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. Increasing evidence suggests that MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-provoked tissue degeneration. Meanwhile, cancer cells and cancer stromal cells also cross-talk through mitochondrial exchange to regulate cancer metastasis. This review summarizes the research on MSCs and their mitochondrial transfer. It provides an overview of the biology, function, niches and signaling that play a role in tissue repair. It also highlights the pathologies of cancer growth and metastasis linked to mitochondrial exchange between cancer cells and surrounding stromal cells. It becomes evident that the function of MSC mitochondrial transfer is a double-edged sword. MSC mitochondrial transfer may be a pharmaceutical target for tissue repair and cancer therapy.

scholarly journals NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay

Oncogene ◽  
2021 ◽  
Author(s):  
Lin Zhao ◽  
Longyang Jiang ◽  
Ming Zhang ◽  
Qiang Zhang ◽  
Qiutong Guan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Mrna Stability ◽  
Mrna Decay ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Breast And Ovarian Cancer ◽  
Cell Metastasis

AbstractPrevious study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3′-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3′-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3′-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.

scholarly journals Microenvironment remodeled by tumor and stromal cells elevates fibroblast-derived COL1A1 and facilitates ovarian cancer metastasis

2020 ◽  
Vol 394 (1) ◽  
pp. 112153
Author(s):  
Mingyue Li ◽  
Jiaying Wang ◽  
Conghui Wang ◽  
Lili Xia ◽  
Junfen Xu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stromal Cells ◽  
Cancer Metastasis

To the origin of cancer metastases

1927 ◽  
Vol 23 (1) ◽  
pp. 123-124
Keyword(s):  
Epithelial Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Cancer Metastases ◽  
Single Living

There was a time when one single living cancer cell was considered sufficient for cancer metastasis to occur. Later studies by Rhoda Erdmann proved that transfer, not only of epithelial cells, but also of stromal cells was necessary for the formation of metastasis.

scholarly journals Ovarian cancer: involvement of the matrix metalloproteinases

Reproduction ◽  
2015 ◽  
Vol 150 (2) ◽  
pp. R55-R64 ◽  
Author(s):  
Linah Al-Alem ◽  
Thomas E Curry
Keyword(s):  
Ovarian Cancer ◽  
Matrix Metalloproteinases ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Proteolytic Enzymes ◽  
Gynecologic Malignancies ◽  
Gynecologic Malignancy ◽  
The Matrix ◽  
Current Paradigm ◽  
Ovarian Tumor Cells

Ovarian cancer is the leading cause of death from gynecologic malignancies. One of the reasons for the high mortality rate associated with ovarian cancer is its late diagnosis, which often occurs after the cancer has metastasized throughout the peritoneal cavity. Cancer metastasis is facilitated by the remodeling of the extracellular tumor matrix by a family of proteolytic enzymes known as the matrix metalloproteinases (MMPs). There are 23 members of the MMP family, many of which have been reported to be associated with ovarian cancer. In the current paradigm, ovarian tumor cells and the surrounding stromal cells stimulate the synthesis and/or activation of various MMPs to aid in tumor growth, invasion, and eventual metastasis. The present review sheds light on the different MMPs in the various types of ovarian cancer and on their impact on the progression of this gynecologic malignancy.

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