Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‑associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‑expression of keratins‑8/‑14 in the EM‑G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‑8, ‑14, ‑18, ‑19) and epithelial‑mesenchymal transition‑associated markers (SLUG, SNAIL, ZEB1, E‑/N‑cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‑A and MFGE8 attenuated the modulatory effect of CAFs on EM‑G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‑G3 cells in vitro. CAFs of different origins support the pro‑inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.

• Keywords
• breast cancer, cell differentiation, epithelial‑mesenchymal interaction, neutralizing antibody, tumor microenvironment,
• MeSH
• Antigens, Surface MeSH
• Cancer-Associated Fibroblasts * metabolism   MeSH
• Fibroblasts metabolism   MeSH
• Keratins genetics   metabolism   MeSH
• Humans MeSH
• Melanoma, Cutaneous Malignant MeSH
• MCF-7 Cells MeSH
• Milk Proteins genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Tumor Microenvironment genetics   MeSH
• Breast Neoplasms * drug therapy   genetics   metabolism   MeSH
• Prognosis MeSH
• Transcriptome MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antigens, Surface MeSH
• Keratins MeSH
• MFGE8 protein, human MeSH Browser
• Milk Proteins MeSH

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

• Keywords
• cancer, cytokine, galectin, stem cell, tissue repair,
• MeSH
• Cellular Microenvironment MeSH
• Cytokines metabolism   MeSH
• Galectins metabolism   MeSH
• Wound Healing MeSH
• Immune System cytology   immunology   metabolism   MeSH
• Keloid metabolism   pathology   MeSH
• Humans MeSH
• Intercellular Signaling Peptides and Proteins metabolism   MeSH
• Neoplastic Stem Cells metabolism   pathology   MeSH
• Tumor Microenvironment * MeSH
• Neoplasms immunology   metabolism   pathology   MeSH
• Wounds and Injuries immunology   metabolism   pathology   MeSH
• Signal Transduction * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cytokines MeSH
• Galectins MeSH
• Intercellular Signaling Peptides and Proteins MeSH

Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle-also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.

• Keywords
• cancer microenvironment, cancer-associated fibroblast, niche, stem cell, wound healing,
• MeSH
• Epidermal Cells MeSH
• Epithelial Cells pathology   MeSH
• Fibroblasts pathology   MeSH
• Wound Healing physiology   MeSH
• Keratinocytes pathology   MeSH
• Humans MeSH
• Melanoma pathology   MeSH
• Mesenchymal Stem Cells pathology   MeSH
• Neoplastic Stem Cells pathology   MeSH
• Tumor Microenvironment physiology   MeSH
• Skin Neoplasms pathology   MeSH
• Stem Cell Niche physiology   MeSH
• Hair Follicle cytology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH