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Publications (3 of 3) Show all publications
Lazarczyk, M., Kurzejamska, E., Mickael, M.-E., Poznanski, P., Skiba, D., Sacharczuk, M., . . . Religa, P. (2023). Mouse CCL9 Chemokine Acts as Tumor Suppressor in a Murine Model of Colon Cancer. Current Issues in Molecular Biology, 45(4), 3446-3461
Open this publication in new window or tab >>Mouse CCL9 Chemokine Acts as Tumor Suppressor in a Murine Model of Colon Cancer
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2023 (English)In: Current Issues in Molecular Biology, ISSN 1467-3037, E-ISSN 1467-3045, Vol. 45, no 4, p. 3446-3461Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer is the third most frequently diagnosed cancer in the world. Despite extensive studies and apparent progress in modern strategies for disease control, the treatment options are still not sufficient and effective, mostly due to frequently encountered resistance to immunotherapy of colon cancer patients in common clinical practice. In our study, we aimed to uncover the CCL9 chemokine action employing the murine model of colon cancer to seek new, potential molecular targets that could be promising in the development of colon cancer therapy. Mouse CT26.CL25 colon cancer cell line was used for introducing lentivirus-mediated CCL9 overexpression. The blank control cell line contained an empty vector, while the cell line marked as CCL9+ carried the CCL9-overexpressing vector. Next, cancer cells with empty vector (control) or CCL9-overexpressing cells were injected subcutaneously, and the growing tumors were measured within 2 weeks. Surprisingly, CCL9 contributed to a decline in tumor growth in vivo but had no effect on CT26.CL25 cell proliferation or migration in vitro. Microarray analysis of the collected tumor tissues revealed upregulation of the immune system-related genes in the CCL9 group. Obtained results suggest that CCL9 reveals its anti-proliferative functions by interplay with host immune cells and mediators that were absent in the isolated, in vitro system. Under specific study conditions, we determined unknown features of the murine CCL9 that have so far bee reported to be predominantly pro-oncogenic.

Place, publisher, year, edition, pages
MDPIMDPI AG, 2023
Keywords
CCL9, chemokine, CCR1, colon cancer
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-501979 (URN)10.3390/cimb45040226 (DOI)000977530000001 ()37185750 (PubMedID)
Available from: 2023-05-22 Created: 2023-05-22 Last updated: 2024-01-15Bibliographically approved
Lazarczyk, M., Mickael, M. E., Skiba, D., Kurzejamska, E., Lawinski, M., Horbanczuk, J. O., . . . Sacharczuk, M. (2023). The Journey of Cancer Cells to the Brain: Challenges and Opportunities. International Journal of Molecular Sciences, 24(4), Article ID 3854.
Open this publication in new window or tab >>The Journey of Cancer Cells to the Brain: Challenges and Opportunities
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2023 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 4, article id 3854Article, review/survey (Refereed) Published
Abstract [en]

Cancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood-brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better understanding of the metastasis process to uncover novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the diverse processes that they undergo to colonize the brain. These processes include EMT, intravasation, extravasation, and infiltration of the blood-brain barrier, ending up with colonization and angiogenesis. In each phase, we focus on the pathways engaging molecules that potentially could be drug target candidates.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
brain, metastasis, cancer, immune cells
National Category
Cancer and Oncology Neurosciences
Identifiers
urn:nbn:se:uu:diva-500098 (URN)10.3390/ijms24043854 (DOI)000945051900001 ()36835266 (PubMedID)
Available from: 2023-04-12 Created: 2023-04-12 Last updated: 2023-04-12Bibliographically approved
Mader, T., Chaillou, T., Alves, E. S., Jude, B., Cheng, A. J., Kenne, E., . . . Lanner, J. T. (2022). Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer. Journal of Cachexia, Sarcopenia and Muscle, 13(2), 1151-1163
Open this publication in new window or tab >>Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer
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2022 (English)In: Journal of Cachexia, Sarcopenia and Muscle, ISSN 2190-5991, E-ISSN 2190-6009, Vol. 13, no 2, p. 1151-1163Article in journal (Refereed) Published
Abstract [en]

Background Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality and disease recurrence. However, the molecular processes underlying breast cancer-induced muscle weakness and the beneficial effect of exercise are largely unknown. Methods Eight-week-old breast cancer (MMTV-PyMT, PyMT) and control (WT) mice had access to active or inactive in-cage voluntary running wheels for 4 weeks. Mice were also subjected to a treadmill test. Muscle force was measured ex vivo. Tumour markers were determined with immunohistochemistry. Mitochondrial biogenesis and function were assessed with transcriptional analyses of PGC-1 alpha, the electron transport chain (ETC) and antioxidants superoxide dismutase (Sod) and catalase (Cat), combined with activity measurements of SOD, citrate synthase (CS) and beta-hydroxyacyl-CoA-dehydrogenase (beta HAD). Serum and intramuscular stress levels were evaluated by enzymatic assays, immunoblotting, and transcriptional analyses of, for example, tumour necrosis factor-alpha (TNF-alpha) and p38 mitogen-activated protein kinase (MAPK) signalling. Results PyMT mice endured shorter time and distance during the treadmill test (similar to 30%, P < 0.05) and ex vivo force measurements revealed similar to 25% weaker slow-twitch soleus muscle (P < 0.001). This was independent of cancer-induced alteration of muscle size or fibre type. Inflammatory stressors in serum and muscle, including TNF-alpha and p38 MAPK, were higher in PyMT than in WT mice (P < 0.05). Cancer-induced decreases in ETC (P < 0.05, P < 0.01) and antioxidant gene expression were observed (P < 0.05). The exercise intervention counteracted the cancer-induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced beta-HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNF alpha-targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise-induced PGC-1 alpha expression, and CS and beta-HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease. Conclusions Four-week voluntary wheel running counteracted muscle weakness in PyMT mice which was accompanied by reduced intrinsic stress and improved mitochondrial and antioxidant profiles and activities that aligned with muscles of healthy mice.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
Muscle weakness, Breast cancer, Stress, Mitochondria
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-485668 (URN)10.1002/jcsm.12944 (DOI)000755356300001 ()35170227 (PubMedID)
Funder
Swedish Research Council, 2017-03056Swedish Research Council, 2019-01282Karolinska InstituteSwedish Cancer Society, 2018/875
Available from: 2022-09-30 Created: 2022-09-30 Last updated: 2022-09-30Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8050-6516

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