The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression

Cancers, Год журнала: 2024, Номер 16(9), С. 1727 - 1727

Опубликована: Апрель 29, 2024

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays crucial role in driving progression, shaping treatment responses, influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) stroma, highlighting its key constituents their dynamic contributions. We examine how significant changes within cSCC ECM—specifically, alterations fibronectin, hyaluronic acid, laminins, proteoglycans, collagens—promote cancer metastasis, drug resistance. composition TME is also explored, detailing intricate interplay cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, various immune populations. These diverse players modulate development, angiogenesis, responses. Finally, we emphasize TME’s potential as therapeutic target. Emerging strategies discussed this include harnessing system (adoptive transfer, checkpoint blockade), hindering disrupting CAF activity, manipulating ECM components. approaches underscore vital that deciphering interactions advancing therapy. Further research illuminating these relationships will uncover new avenues for developing more effective treatments cSCC.

Язык: Английский

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Mesenchymal stem cells - the secret agents of cancer immunotherapy: Promises, challenges, and surprising twists

Oncotarget, Год журнала: 2024, Номер 15(1), С. 793 - 805

Опубликована: Ноя. 22, 2024

// Theia Minev 1 , Shani Balbuena Jaya Mini Gill Francesco M. Marincola 2 Santosh Kesari 3 and Feng Lin CureScience Institute, San Diego, CA 92121, USA Sonata Therapeutics, Boston, MA 02472, Department of Translational Neurosciences, Pacific Neuroscience Institute Providence Saint John's Health Center, Cancer Santa Monica, 90404, Correspondence to: Lin, email: [email protected] Keywords: mesenchymal stem cells; genetic engineering; cancer immunotherapy; cell homing; delivery Received: August 20, 2024 Accepted: November 05, Published: 22, Copyright: © et al. This is an open access article distributed under the terms Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, reproduction in any medium, provided original author source are credited. ABSTRACT Mesenchymal cells (MSCs) recognized for their immunomodulatory capabilities, tumor-homing abilities, capacity to serve as carriers therapeutic agents. review delves into role adoptively transferred MSCs tumor progression, interactions with microenvironment, use delivering anti-cancer drugs, oncolytic viruses, material. It also addresses challenges limitations associated MSC therapy, such variability preparations potential tumorigenic effects emphasizing need advanced engineering personalized approaches enhance efficacy. The concludes optimistic outlook on future MSC-based therapies, underscoring promise develop effective treatments.

Язык: Английский

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Impact of Minimally Manipulated Cell Therapy on Immune Responses in Radiation-Induced Skin Wound Healing

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1994 - 1994

Опубликована: Фев. 25, 2025

The current treatment of radiation-induced skin wounds utilizes mainly conventional therapies, including topical steroids, creams, ointments, and hydrogel dressings, which do not take into account the immunologic changes that occur in after radiation exposure. Therefore, it is relevant to consider alternative therapies their impact on immune landscape skin. aim this study was investigate effect allogeneic minimally manipulated keratinocytes fibroblasts rat repair development responses. We found use cell therapy compared with syntazone ointment no resulted faster healing a reduction size wounds, area inflammation, edema. Additionally, group receiving application, there an observed increase number mast cells (MCs), activation MC interaction M2 macrophages, direct contact MCs vascular bed, content collagen fibers due intensification fibrillogenesis, restoration histotopographic organization. Thus, positive based regeneration indicated can be used clinical practice improve effectiveness rehabilitation therapy.

Язык: Английский

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Homeostasis and evolution in relation to regeneration and repair

The Journal of Physiology, Год журнала: 2024, Номер 602(11), С. 2627 - 2648

Опубликована: Май 23, 2024

Homeostasis constitutes a key concept in physiology and refers to self-regulating processes that maintain internal stability when adjusting changing external conditions. It diminishes entropy constituting driving force behind evolution. Natural selection might act on homeostatic regulatory mechanisms control including homeodynamics, allostasis, hormesis homeorhesis, where different stable stationary states are reached. Regeneration is under through hormesis. Damage tissues initiates response restore the impaired equilibrium caused by mild stress using cell proliferation, differentiation death recover structure function. Repair homeorhetic change leading new state with decreased functionality fibrotic scarring without reconstruction of 3-D pattern. Mechanisms determining entrance tissue or organ regeneration repair include balance between innate adaptive immune cells relation plasticity stromal stem responses, redox balance. The regenerative reparative capacities vary species, distinct organs, at stages development ageing. Many signals pathways play crucial roles regulating protein synthesis, cellular growth, inflammation, autophagy, lysosomal function, metabolism metalloproteinase signalling. Attempts favour damaged those low proliferative rates have been made; however, there evolutionary constraint poor proliferation unfavourable environments tumour development. More research required better understand these mechanisms.

Язык: Английский

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Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

Biomolecules, Год журнала: 2024, Номер 14(7), С. 734 - 734

Опубликована: Июнь 21, 2024

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential regulation tissue repair and homeostasis, immune modulation. However, use cancer therapy is controversial: they can inhibit proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation milieu increasing stem invasiveness. This opposite behaviour highlights need for careful nuanced MSCs treatment. To optimize anti-cancer effects, diverse strategies have bioengineered enhance targeting properties or deliver drugs. In this review, we highlight uses therapy, particularly as carriers targeted treatments natural tumour-homing capabilities. We discuss MSC-derived extracellular vesicles improve efficiency drug molecule delivery cells. Ongoing clinical trials evaluating these setting stage future advances MSC-based It critical identify broad potent applications solid agent position them effective therapeutics evolving field therapy.

Язык: Английский

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Converging frontiers in cancer treatment: the role of nanomaterials, mesenchymal stem cells, and microbial agents—challenges and limitations

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 21, 2024

Globally, people widely recognize cancer as one of the most lethal diseases due to its high mortality rates and lack effective treatment options. Ongoing research into therapies remains a critical area inquiry, holding significant social relevance. Currently used treatment, such chemotherapy, radiation, or surgery, often suffers from other problems like damaging side effects, inaccuracy, ability clear tumors. Conventional are usually imprecise ineffective develop resistance treatments recurs. Cancer patients need fresh innovative that can reduce effects while maximizing effectiveness. In recent decades several breakthroughs in these, areas medical research, have paved way for new avenues fighting including more focused alternatives. This study reviews exciting possibilities mesenchymal stem cells (MSCs), nanomaterials, microbial agents modern realm treatment. Nanoparticles (NPs) demonstrated surprisingly potential. They improve drug delivery systems (DDS) significantly, enhance imaging techniques remarkably, target selectively protecting healthy tissues. MSCs play double role tissue repair vehicle novel gene NPs loaded with therapeutic agents. Additionally, utilizing agents, particularly those involving bacteria, offer an inventive approach review investigates potential MSCs, addressing shortcomings conventional therapies. We will also discuss challenges limitations using these approaches.

Язык: Английский

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Mesenchymal stem cell-mediated adipogenic transformation: a key driver of oral squamous cell carcinoma progression

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 23, 2025

Язык: Английский

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Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 4, 2025

A large body of evidence suggests that mesenchymal stromal cells (MSCs) are able to respond rapidly the cytokine milieu following systemic infusion. This encounter has potential dictate their therapeutic efficacy (also referred as licensing). MSCs react cellular damage by migrating inflamed tissue and ultimately modifying inflammatory microenvironment. However, limited use in clinical practice can be attributed a lack understanding fate patients after administration long term MSC-derived activity. While known physiological effectors viable make relative contribution, an innate property agent is caspase-dependent cell death. These mechanisms may involving functional reprogramming myeloid phagocytes via efferocytosis, process which apoptotic bodies (ABs) identified for engulfment both specialized non-specialized phagocytic cells. Recent studies have provided uptake ABs with distinct genetic component induce changes gene expression through epigenetic remodeling. phenomenon, 'trained immunity', significant impact on immunometabolism processes. It hypothesized diversity recipient within stroma adjacent potentially serve biomarker predicting outcome MSC treatment, while also contributing variable outcomes observed MSC-based therapies. Therefore, long-term reconstructive mediated apoptosis subsequent phagocyte-mediated efferocytosis.

Язык: Английский

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Mesenchymal stem cells modulate breast cancer progression through their secretome by downregulating ten-eleven translocation 1

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 24, 2025

Mesenchymal stem cells (MSCs) have emerged as crucial players within the tumor microenvironment (TME), contributing through their paracrine secretome. Depending on context, MSC-derived secretome can either support or inhibit growth. This study investigates role of in modulating breast cancer (BC) cell behavior, with a focus ten-eleven translocation 1 (TET1), DNA demethylase known oncogenic properties triple-negative (TNBC). We first isolated and characterized human bone marrow-derived MSCs, then assessed impact BC cells. Treatment significantly inhibited proliferation migration both MDA-MB-231 MCF-7 lines, resulting reduced viability rates compared to control Western blot analyses revealed downregulation Cyclin D1 c-Myc, along decreased expression N-cadherin increased E-cadherin, indicating potential inhibition epithelial-to-mesenchymal transition. Differential gene highlighted TET1 upregulated TNBC tissues normal samples. Further experiments confirmed that downregulated cells, evidenced by RT-qPCR western analyses. To explore TET1's functional role, we silenced siRNAs, observing cycle arrest enhanced apoptosis—effects mirrored those seen MSC-secretome treatment. Notably, knockdown also sensitivity cisplatin, suggesting for chemoresistance. These findings provide insight into ability MSCs modulate progression secretome, highlighting involvement inhibiting enhancing cisplatin chemosensitivity. The thus holds promise an innovative, cell-free therapeutic approach

Язык: Английский

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Study on the efficacy of IFN-γ- and sPD-1-overexpressing BMSCs in enhancing immune effects for the treatment of lung adenocarcinoma

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 13, 2025

Background Soluble programmed cell death receptor-1 (sPD-1) blocks the PD-1/PD-L1 pathway, reverses tumor immune suppression, and inhibits growth. However, clinical applications are limited by its poor tissue distribution rapid dispersion. Bone marrow-derived mesenchymal stem cells (BMSCs) favorable carriers for immunotherapy due to their capacity external gene introduction targeted homing. they may inadvertently promote Interferon-gamma (IFN-γ) BMSC-mediated growth stimulates antigen-presenting activate T lymphocytes. This study utilizes BMSCs transfected with IFN-γ as sPD-1, enabling homing of sPD-1 tissues, thereby enhancing efficacy sustained stability immunotherapy. Methods stable IFN-γ- sPD-1-overexpressing were successfully constructed lentiviral transfection. A non-contact co-culture system was established Lewis A549 lung adenocarcinoma observe changes in cancer after co-culture, using assays including migration invasion experiments, well cellular senescence detection. Additionally, a subcutaneous model C57BL/6J mice intervention studies. Tumor volume, apoptosis (assessed TUNEL assay), peripheral Treg (analyzed flow cytometry), histopathological markers (evaluated HE staining immunohistochemistry) analyzed. The expression levels BAX, BCL-2, AKT, PI3K, PD-L1 assessed quantitative PCR Western Blot. Results exhibited high bioactivity genetic stability, inhibiting proliferation, accelerating senescence, reducing invasion. Furthermore, upregulate Bax expression, downregulate Bcl-2, apoptosis. these alleviate inflammatory damage tumor-bearing mice, lower inhibit evasion, reduce PI3K/AKT PD-L1. Conclusion effectively progression. primary mechanisms include suppression growth, migration, invasion; promotion cells; modulation inhibition signaling pathway pathways.

Язык: Английский

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