scholarly journals When dormancy fuels tumour relapse

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Karla Santos-de-Frutos ◽  
Nabil Djouder
Keyword(s):  
Cell Cycle ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Tumour Growth ◽  
Growth Arrest ◽  
Tumour Microenvironment ◽  
Review Article ◽  
Paracrine Signalling ◽  
Quiescent Cells ◽  
Tumour Relapse

AbstractTumour recurrence is a serious impediment to cancer treatment, but the mechanisms involved are poorly understood. The most frequently used anti-tumour therapies—chemotherapy and radiotherapy—target highly proliferative cancer cells. However non- or slow-proliferative dormant cancer cells can persist after treatment, eventually causing tumour relapse. Whereas the reversible growth arrest mechanism allows quiescent cells to re-enter the cell cycle, senescent cells are largely thought to be irreversibly arrested, and may instead contribute to tumour growth and relapse through paracrine signalling mechanisms. Thus, due to the differences in their growth arrest mechanism, metabolic features, plasticity and adaptation to their respective tumour microenvironment, dormant-senescent and -quiescent cancer cells could have different but complementary roles in fuelling tumour growth. In this review article, we discuss the implication of dormant cancer cells in tumour relapse and the need to understand how quiescent and senescent cells, respectively, may play a part in this process.

QS301. Apigenin Potentiates Gemcitabine-Induced Growth Arrest of Pancreatic Cancer Cells Through Blocking of Gemcitabine-Induced Upregulation of Cell Cycle Proteins

2008 ◽  
Vol 144 (2) ◽  
pp. 387
Author(s):  
Matthew J. Strouch ◽  
Benjamin M. Milam ◽  
Laleh G. Melstrom ◽  
Mohammad R. Salabat ◽  
Daniel M. Heifferman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Growth Arrest ◽  
Cell Cycle Proteins ◽  
Pancreatic Cancer Cells

scholarly journals Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments

2019 ◽  
Vol 2 (3) ◽  
pp. e201900304 ◽  
Author(s):  
Ulrich Blache ◽  
Edward R Horton ◽  
Tian Xia ◽  
Erwin M Schoof ◽  
Lene H Blicher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Breast Cancer Cells ◽  
Cell Activation ◽  
Tumour Microenvironment ◽  
Paracrine Signalling ◽  
Organ Specific ◽  
Mcf 7

Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global approaches. Using mass spectrometry, we compared the secretomes of MCF-7 cells, invasive MDA-MB-231 cells, and sublines isolated from bone, lung, and brain metastases and identified ECM and exosome components associated with invasion and organ-specific metastasis. Next, we used synthetic hydrogels to investigate how these different secretomes activate MSCs in bioengineered 3D microenvironments. Using kinase activity profiling and RNA sequencing, we found that only MDA-MB-231 breast cancer secretomes convert MSCs into TA-MSCs, resulting in an immunomodulatory phenotype that was particularly prominent in response to bone-tropic cancer cells. We have investigated paracrine signalling from breast cancer cells to TA-MSCs in 3D, which may highlight new potential targets for anticancer therapy approaches aimed at targeting tumour stroma.

scholarly journals Combination of Tangeretin and 5-Fluorouracil Modulates Cell Cycle and Induce Apoptosis on WiDr Cells

2012 ◽  
Vol 3 (1) ◽  
pp. 364
Author(s):  
Luthfia Indriyani ◽  
Adam Hermawan ◽  
Riris Istighfari Jenie
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Cytotoxic Effect ◽  
Annexin V ◽  
Potential Effect ◽  
Apoptosis Induction ◽  
Cell Cycle Modulation

Co-chemotherapeutics approaches are increasing in cancer treatment in order mainly to suppress the resistence phenomenon of cancer treatment and to enhance the cytotoxic effect of the main chemotherapeutics agent. Tangeretin has been known to have cytotoxic effect to some cancer cells through some pathways in the cells. To explore the potential effect of tangeretin as co-chemotherapeutics agent this research was subjected to study the cytotoxic effect of tangeretin in combination with 5-Fluoro Uracil (5-FU) on WiDr colon cancer cells covering the modulation of cell cycle and apoptosis induction. Cytotoxic effect was examined by using MTT assay while apoptotis induction was determined by annexin-V flowcytometry. Under MTT assay, tangeretin showed weak cytotoxic activity on the cells. However, tangeretin significantly enhanced the cytotoxic effect of 5-FU on the cells. This co-chemotherapeutics effect likely correlated with cell cycle modulation effect, especially in inducing polyploidy phenomenon as expressed in the flowcytometric graph of the DNA content. This combination also increased apoptosis induction. These result suggest that tangeretin is potential to be developed as co-chemotherapeutic agent for 5-Fu on colon cancer and further molecular mechanism need to be explored.Keywords: Tangeretin, 5-Fluorourasil, WiDr, cell cycle, apoptosis.

scholarly journals Primary and Compensatory Roles for RB Family Members at Cell Cycle Gene Promoters That Are Deacetylated and Downregulated in Doxorubicin-Induced Senescence of Breast Cancer Cells

2006 ◽  
Vol 26 (7) ◽  
pp. 2501-2510 ◽  
Author(s):  
James G. Jackson ◽  
Olivia M. Pereira-Smith
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Drug Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Arrest ◽  
S Phase ◽  
Cyclin B ◽  
Cell Cycle Gene ◽  
Gene Promoters

ABSTRACT When treated with DNA-damaging chemotherapy agents, many cancer cells, in vivo and in vitro, undergo a terminal growth arrest and acquire a senescence-like phenotype. We investigated the molecular basis for this in breast cancer cells following a 2-hour treatment with 1 μM doxorubicin. Treated cells arrested in G1 and G2 phases of the cell cycle, with concomitant reductions in S-phase and G2-M regulatory genes. p53 and p21 protein levels increased within hours after treatment and were maintained for 5 to 6 days but were reduced 8 days posttreatment, though the cells remained growth arrested. Levels of p130 rose after drug treatment, and it was the primary RB family member recruited to the S-phase promoters cyclin A and PCNA and G2-M promoters cyclin B and cdc2, remaining present for the entire 8-day time period. In contrast, p107 protein and promoter occupancy levels declined sharply after drug treatment. RB was recruited to only the PCNA promoter. In MCF-7 cells with p130 knockdown, p107 compensated for p130 loss at all cell cycle gene promoters examined, allowing cells to retain the growth arrest phenotype. Cells with p130 and p107 knockdown similarly arrested, while cells with knockdown of all three family members failed to downregulate cyclin A and cyclin B. These results demonstrate a mechanistic role for p130 and compensatory roles for p107 and RB in the long-term senescence-like growth arrest response of breast cancer cells to DNA damage.

scholarly journals Increased Expression of Cyclin D2 during Multiple States of Growth Arrest in Primary and Established Cells

1998 ◽  
Vol 18 (6) ◽  
pp. 3163-3172 ◽  
Author(s):  
Muthupalaniappan Meyyappan ◽  
Howard Wong ◽  
Christopher Hull ◽  
Karl T. Riabowol
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Growth Arrest ◽  
Growth Conditions ◽  
Cellular Growth ◽  
Serum Starvation ◽  
Cyclin D2 ◽  
Cycle Progression ◽  
Quiescent Cells ◽  
D2 Protein

ABSTRACT Cyclin D2 is a member of the family of D-type cyclins that is implicated in cell cycle regulation, differentiation, and oncogenic transformation. To better understand the role of this cyclin in the control of cell proliferation, cyclin D2 expression was monitored under various growth conditions in primary human and established murine fibroblasts. In different states of cellular growth arrest initiated by contact inhibition, serum starvation, or cellular senescence, marked increases (5- to 20-fold) were seen in the expression levels of cyclin D2 mRNA and protein. Indirect immunofluorescence studies showed that cyclin D2 protein localized to the nucleus in G0, suggesting a nuclear function for cyclin D2 in quiescent cells. Cyclin D2 was also found to be associated with the cyclin-dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest. Cyclin D2-CDK2 complexes increased in amounts but were inactive as histone H1 kinases in quiescent cells. Transient transfection and needle microinjection of cyclin D2 expression constructs demonstrated that overexpression of cyclin D2 protein efficiently inhibited cell cycle progression and DNA synthesis. These data suggest that in addition to a role in promoting cell cycle progression through phosphorylation of retinoblastoma family proteins in some cell systems, cyclin D2 may contribute to the induction and/or maintenance of a nonproliferative state, possibly through sequestration of the CDK2 catalytic subunit.

scholarly journals CHANGES IN EXPRESSION OF CELL CYCLE-ASSOCIATED GENES ACCOMPANY RETINOIC ACID-INDUCED GROWTH ARREST IN PANCREATIC CANCER CELLS.

Pancreas ◽  
2004 ◽  
Vol 29 (4) ◽  
pp. 334
Author(s):  
B. Singh ◽  
A. Roginsky ◽  
X.-Z. Ding ◽  
R.F. Murphy ◽  
M.S. Talamonti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Growth Arrest ◽  
Pancreatic Cancer Cells
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