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New insights into STE biology are expanding opportunities for earlier detection and more effective therapy, especially via molecular imaging innovations and real-time skin fluorescent imaging 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Diagnosis and Treatment  \nFrank Jing1  | Ani Pazhava1  | Catherine Shachaf2  | Alexander Meves1   \n1Department of Dermatology, Mayo Clinic, Rochester, Minnesota, USA | 2Orlucent Inc. , Los Gatos, California, USA Correspondence: Catherine Shachaf ([cshachaf@orlucent.com](cshachaf@orlucent.com))  \nReceived: 5 February 2025 | Revised: 13 April 2025 | Accepted: 18 April 2025  \nFunding: The authors received no specific funding for this work.  \nKeywords: αvβ3 integrin | in vivo imaging | melanoma | nevus | review | stroma | tissue remodeling | tumor microenvironment  \nABSTRACT  \nThe stromal tumor environment (STE) plays a vital yet often underrecognized role in cancer progression, shaping tumor development. It influences complex interactions among stromal cells, immune cells, extracellular matrix (ECM) components, and signaling molecules. Stromal cells regulate integrin signaling and are involved in remodeling the tumor microenvironment, driving critical processes such as cell migration, survival, angiogenesis, and proliferation. Advances in understanding the STE are creating new opportunities for early cancer detection and treatment. Innovations in molecular imaging, particularly for melanoma, are transforming cancer diagnostics by providing deeper insights into tumor biology, cellular interactions, and angiogenesis, paving the way for more personalized and timely therapeutic interventions. Among these advancements, in vivo skin fluorescent imaging (SFI) stands out as a powerful tool, offering real-time molecular insights at the point of care with the ability to improve patient management.  \n1 | Introduction  \nCancer development arises from a complex interplay of genetic alterations and interactions between tumor cells and their surrounding environment. Among these influences, the stromal tumor environment (STE)—a highly organized and dynamic ecosystem—plays a pivotal yet underrecognized role in cancer initiation and progression [1] .  \nThe importance of the STE was first established in the 1970s when Folkman demonstrated that the growth of tumor microfoci was limited by oxygen diffusion distance from nearby capillaries,  \napproximately 250 μm [2]. Without the formation of new blood vessels—neoangiogenesis—most microfoci remain dormant at a size of 1–2 mm3 and are clinically inconsequential. This seminal finding emphasized the critical role of structural and functional remodeling within the STE as a prerequisite for tumor development.  \nThe STE facilitates tumor initiation and drives cancer progression through mechanisms that enhance cell survival, invasion, and migration [1, 3]. It comprises a diverse array of cellular and acellular components, including immune cells, fibroblasts, endothelial cells, pericytes, and adipocytes, all embedded within a remodeled and vascularized extracellular matrix (ECM) [4] .  \n\n| Abbreviations: CAFs, cancer-associated fibroblasts; CN, benign/common nevi; DN, atypical/dysplastic nevi; ECM, extracellular matrix; ECs, endothelial cells; EGF, epidermal growth factor; EIS, electrical impedance spectroscopy; EMT, epithelial-mesenchymal transition; GEP, gene expression profiling; HIFs, hypoxia-inducible factors; IHC, immunohistochemistry; MET, metastatic melanoma; MIS, melanoma in situ; MIS, melanoma in situ (MIS) to; MMPs, matrix metalloproteases; MPM, multiphoton microscopy; MRI, magnetic resonance imaging; MSI, multispectral imaging; OCT, optical coherence tomography; PAI, photoacoustic imaging; PET, positron emission tomography; RCM, reflectance confocal microscopy; RGD, arginine-glycine-aspartic acid; RGP, radial growth phase; SFI, skin fluorescent imaging; STE, stromal tumor environment; TAMs, tumor-associated macrophages; Tregs, regulatory t-cells; VEGF, vascular endothelial growth factor; VGP, vertical growth phase. |\n| --- |\n| This is an open access article under the terms of th","cbCaijfGWlm0FnSL","https://ap.wps.com/l/cbCaijfGWlm0FnSL","pdf",659879,"English","# Introduction\n# Cancer Progression in the STE\n# (Implied) Imaging and Clinical Translation","[{\"question\":\"What role does the stromal tumor environment (STE) play in skin cancer progression?\",\"answer\":\"The STE shapes tumor development by coordinating interactions among stromal cells, immune cells, ECM components, and signaling molecules, and it drives processes such as migration, survival, angiogenesis, and proliferation.\"},{\"question\":\"How do stromal cells contribute to tumor behavior?\",\"answer\":\"Stromal cells regulate integrin signaling and remodel the tumor microenvironment, which supports key steps including cell migration, survival, angiogenesis, and proliferation.\"},{\"question\":\"Why is in vivo skin fluorescent imaging (SFI) important for diagnosis and treatment?\",\"answer\":\"SFI provides real-time molecular insights at the point of care, helping improve patient management and enabling earlier, more personalized interventions by revealing tumor biology and related cellular interactions.\"}]","The Role of Stromal Tumor Environment in Advancing Skin Cancer Diagnosis and Treatment | PDF",1790190948,25]