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Patient-derived sca...
Patient-derived scaffolds representing breast cancer microenvironments influence chemotherapy responses in adapted cancer cells consistent with clinical features.
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- Leiva, Maria Carmen (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine
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- Gustafsson, Anna (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine
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- Garre, Elena, 1978 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine
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- Ståhlberg, Anders, 1975 (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Centrum för Cancerforskning (SCCR),Department of Laboratory Medicine,Sahlgrenska Center for Cancer Research (SCCR)
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Kovács, Anikó (author)
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- Helou, Khalil, 1966 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Oncology
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- Landberg, Göran, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Centrum för Cancerforskning (SCCR),Department of Laboratory Medicine,Sahlgrenska Center for Cancer Research (SCCR)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Journal of translational medicine. - 1479-5876. ; 21:1
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Abstract
Subject headings
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- The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing.PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments. Cancer cell responses to the treatments were monitored by RNA-analyses, highlighting changes in gene sets representative for crucial tumor biological processes such as proliferation, cancer stem cell features, differentiation and epithelial-to-mesenchymal transition.The chemotherapy treatments induced distinct gene expression patterns in adapted cancer cells with clusters of similar treatment responses depending on the patient-derived cancer microenvironment used as growth substrate. The doxorubicin treatment displayed a favorable gene signature among surviving cancer cells with low proliferation (MKI67) and pluripotency features (NANOG, POU5F1), in comparison to 5-fluorouracil showing low proliferation but increased pluripotency. Specific gene changes monitored post-treatment were also significantly correlated with clinical data, including histological grade (NANOG), lymph node metastasis (SLUG) and disease-free patient survival (CD44).This laboratory-based treatment study using patient-derived scaffolds repopulated with cancer cell lines, clearly illustrates that the human cancer microenvironment influences chemotherapy responses. The differences in treatment responses defined by scaffold-cultures have potential prognostic and treatment predictive values.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences (hsv//eng)
Keyword
- Humans
- Female
- Tumor Microenvironment
- Breast Neoplasms
- drug therapy
- Antineoplastic Agents
- pharmacology
- therapeutic use
- Doxorubicin
- pharmacology
- therapeutic use
- Fluorouracil
- pharmacology
- therapeutic use
- Cell Line
- Tumor
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Leiva, Maria Car ...
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Gustafsson, Anna
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Garre, Elena, 19 ...
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Ståhlberg, Ander ...
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Kovács, Anikó
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Helou, Khalil, 1 ...
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Landberg, Göran, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Other Medical an ...
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Journal of trans ...
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University of Gothenburg