Stromal fibroblasts from basal cell carcinoma affect phenotype of normal keratinocytes

Lacina, Lukáš; Smetana, Karel; Dvořánková, Barbora; Pytlík, Robert; Kideryová, L; Kučerová, Lenka; Plzáková, Zuzana; Štork, Jiří; Gabius, Hans‐Joachim; André, Sabine

doi:10.1111/j.1365-2133.2006.07728.x

Cited by 50 publications

(65 citation statements)

References 40 publications

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“…They were allowed to adhere for 15 min on the surface of preseeded cover glasses and all non-adherent cells were washed out. The cells were cultivated in the keratinocyte medium at 37˚C and 3.3% CO 2 (22). Keratinocytes cocultured with 3T3 fibroblasts under the same conditions were used as a control.…”

Section: Methodsmentioning

confidence: 99%

“…To distinguish between the effect of direct contact of the keratinocytes with experimental TC-1 fibroblasts and the role of the medium conditioned by their products, we evaluated the phenotype of keratinocytes separated from the fibroblasts during their coculture by a microporous membrane (Transwell Inserts, Corning, Acton, USA) as described (22).…”

Section: Methodsmentioning

confidence: 99%

“…normal hair follicle (NHF) and normal interfollicular epidermal (NIF) keratinocytes, cultured under the influence of TC-1 cells was monitored and compared with the phenotype of the same cells cultured on a mouse 3T3 cell standard feeder (29). These cells are also of mouse origin and are known to support the growth and physiological differentiation pattern in the normal human keratinocytes under in vitro conditions (22,23).…”

Section: Introductionmentioning

confidence: 99%

“…The impact of stromal cells on the tumor elements was observed predominantly in breast (18), prostate gland (19,20) and colon cancer (21). The fibroblasts isolated from basal or squamous cell carcinoma are able to influence significantly the phenotype of cocultured normal interfollicular keratinocytes to be similar to the phenotype of malignant epithelial tumor cells from which the ONCOLOGY REPORTS 20: 75-80, 2008 75 Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study stromal cells were prepared (22,23). Although the molecular mechanism of the stromal cell action to cancer cells is not clear, the role of specific growth factors/cytokines can be expected because the direct contact between stromal and epithelial cells is not necessary (22,23).…”

Section: Introductionmentioning

confidence: 99%

“…The fibroblasts isolated from basal or squamous cell carcinoma are able to influence significantly the phenotype of cocultured normal interfollicular keratinocytes to be similar to the phenotype of malignant epithelial tumor cells from which the ONCOLOGY REPORTS 20: 75-80, 2008 75 Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study stromal cells were prepared (22,23). Although the molecular mechanism of the stromal cell action to cancer cells is not clear, the role of specific growth factors/cytokines can be expected because the direct contact between stromal and epithelial cells is not necessary (22,23). The nature of tumor-associated fibroblasts is not clear as yet, but in principle they can arise from three different mechanisms or their combination: i) the cytokine/growth factors produced by the malignant cells can influence the local fibroblast population that will consequently support the growth of cancer cells (21); ii) the cancer cells can fuse with the local fibroblasts and form polyploid stromal elements (24) and iii) the direct formation of stromal fibroblasts by the epithelial-mesenchymal transition of malignant epithelium to fibroblastoid stromal cells (25).…”

Section: Introductionmentioning

confidence: 99%

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Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study

Smetana¹,

Dvořánková²,

Lacina³

et al. 2008

Oncol Rep

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Abstract. The role of stem cells in cancer formation and spreading has been established. As with normal tissue, the cancer stem cells need a special microenvironment to support their growth. This microenvironment may be represented by the tumor stroma. One of the possible ways of tumor stromal formation is the epithelial-mesenchymal transition of tumor epithelium. Following this mechanism, stromal cells must share the basic genetic alterations with the tumor cells. In an attempt to create a system capable of testing some aspects of the mesenchymal cell-keratinocyte interactions, we studied the effects of the fibroblastoid mouse TC-1 cells that were prepared by the introduction of human papillomavirus type 16 (HPV16) genes E6 and E7 to lung epithelial cells on the phenotype of normal human interfollicular and hair follicle keratinocytes. From this point of view, they may resemble stromal cells formed by the epithelial-mesenchymal transition of cells from HPV-induced squamous cell carcinoma. In contrast to 3T3 murine embryonic fibroblasts which were used as control cells, TC-1 cells influenced not only the size of the keratinocytes and the shape of their colonies, but also induced the expression of keratins 8 and 19 and vimentin. In conclusion, TC-1 cells exhibited a marked biological activity by influencing the behavior of the normal human follicular and intefollicular keratinocytes. This observation is compatible with the hypothesis that stromal cells play an important role in tumor progression and spreading.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study

Smetana¹,

Dvořánková²,

Lacina³

et al. 2008

Oncol Rep

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Synthetic Polyamine BPA‐C8 Inhibits TGF‐β1‐Mediated Conversion of Human Dermal Fibroblast to Myofibroblasts and Establishment of Galectin‐1‐Rich Extracellular Matrix in Vitro

Mifkova¹,

Kodet²,

Szabó³

et al. 2014

ChemBioChem

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Cancer-associated fibroblasts (CAFs) play a role in the progression of malignant tumors. They are formed by conversion of fibroblasts to smooth muscle α-actin-positive (SMA-positive) myofibroblasts. Polyamines are known to change the arrangement of the actin cytoskeleton by binding to the anionic actin. We tested the effect of the synthetic polyamine BPA-C8 on the transition of human dermal fibroblasts to myofibroblasts induced either by TGF-β1 alone or by TGF-β1 together with adhesion/growth-regulatory galectin-1. Pre-existing CAFs, myofibroblasts from pancreatitis, and rat smooth muscle cells were also exposed to BPA-C8. BPA-C8 impaired myofibroblast formation from activated fibroblasts, but it had no effect on cells already expressing SMA. BPA-C8 also reduced the occurrence of an extracellular matrix around the activated fibroblasts. The reported data thus extend current insights into polyamine activity, adding interference with tumor progression to the tumor-promoting processes warranting study.

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Smooth muscle actin‐expressing stromal fibroblasts in head and neck squamous cell carcinoma: Increased expression of galectin‐1 and induction of poor prognosis factors

Valach

Fík

Strnad

et al. 2012

Intl Journal of Cancer

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Tumor stroma is an active part influencing the biological properties of malignancies via molecular cross-talk. Cancer-associated fibroblasts play a significant role in this interaction. These cells frequently express smooth muscle actin and can be classified as myofibroblasts. The adhesion/growth-regulatory lectin galectin-1 is an effector for their generation. In our study, we set the presence of smooth muscle actin-positive cancer-associated fibroblasts in relation to this endogenous lectin and an in vivo competitor (galectin-3). In squamous cell carcinomas of head and neck, upregulation of galectin-1 presence was highly significantly correlated to presence of smooth muscle actin-positive cancer-associated fibroblasts in the tumor (p 5 4 3 10 28 ). To pinpoint further correlations on the molecular level, we applied microarray analyses to the transcription profiles of the corresponding tumors. Significant correlations of several transcripts were detected with the protein level of galectin-1 in the cancer-associated fibroblasts. These activated genes (MAP3K2, TRIM23, PTPLAD1, FUSIP1, SLC25A40 and SPIN1) are related to known squamous-cell-carcinoma poor-prognosis factors, NF-jB upregulation and splicing downregulation. These results provide new insights into the significance of presence of myofibroblasts in squamous cell carcinoma.Increasing attention is being turned to the stroma part in carcinomas. It is formed by fibroblasts producing the extracellular matrix, macrophages and other inflammatory cells as well as blood/lymphatic capillaries. 1 Recent progress in cancer and skin cell biology has markedly changed our view on the functional significance of the stroma. Classically, the tumor stroma has been considered as a milieu suitable for growth of capillaries that guarantee the supply with oxygen and nutrients for the cancer epithelium. With the new data being accrued, the stroma can be described as an active microenvironment, which modulates the biology of the tumor including cancer stem (initiating) cells by mechanisms similar to the function of the niche in the case of tissue stem cells. 2 As a consequence, a focus of this research is given to the study of mutual epithelial-mesenchymal interactions. This interplay is known to be crucial for embryonic development, and a major role in the route of tumor progression is likely. 2,3 The fibroblasts of the stroma, that is, cancer-associated fibroblasts (CAF), frequently contain fibers of smooth muscle a-actin (SMA and ACTA2), showing notable similarities to myofibroblasts responsible for the contraction of a wound in the course of a healing process. 4 The origin of CAF is not

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Stromal fibroblasts from basal cell carcinoma affect phenotype of normal keratinocytes

Abstract: These observations indicate that BCCFs may differ from normal fibroblasts and may play a regulatory role in BCC biology.

Cited by 50 publications

References 40 publications

Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study

Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: An in vitro study

Synthetic Polyamine BPA‐C8 Inhibits TGF‐β1‐Mediated Conversion of Human Dermal Fibroblast to Myofibroblasts and Establishment of Galectin‐1‐Rich Extracellular Matrix in Vitro

Smooth muscle actin‐expressing stromal fibroblasts in head and neck squamous cell carcinoma: Increased expression of galectin‐1 and induction of poor prognosis factors

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