L.A. Naleskina, N.Y. Lukianova, T.V. Zadvornyi, L.M. Kunska, O.M. Mushii, V.F. Chekhun
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine



Summary. Aim: to determine at the optical level the role of the fibrillar organization of the collagen-containing connective tissue component of the primary tumor focus in prostate cancer (PCa) progression. Objects and methods: the morphological study is based on the analysis of the histological material of the primary tumor foci of 55 PCa patients without tumor progression in the postoperative period and bone metastases. The tumors were graded Gleason 6–9 at surgery. The features of the architecture of collagen-containing connective tissue in tumors were determined in histological slides stained by Van-Gieson. Results: the remodeling of the collagen-containing stromal component located both around the glandular structures (increase in the percentage of straight and aligned collagen fibers compared to the curved ones) and in the stroma itself has been found. Such remodeling is manifested by an increase in the total mass of fibrous structures, an increase in the width of collagen fibrils, their compaction in relation to the density of their location, peculiarities of desmoplasia, alignment and elongation. The specified features are consistent with the Gleason score and the postoperative disease course, namely, the occurrence of metastases. Conclusions: the desmoplastically changed collagen-containing connective tissue component of the PCa creates favorable conditions for the unimpeded migration and realization of the invasive potential of cancer cells, in particular those expressing bone tissue remodeling proteins.

Keywords: prostate cancer, collagen-containing connective tissue architecture, tumor stroma, bone metastases.



  1. Pavlova IP, Nair SS, Lundon D, et al. Multiphoton micros- copy for identifying collagen signatures associated with bio- chemical recurrence in prostate cancer patients. J Pers Med 2021; 11 (11): 106
  2. Zundera SM, Gelderblom H, Tollenaara RA, Mesker WE. The significance of stromal collagen organization in cancer tissue: An in-depth discussion of Crit Rev On- col Hematol 2020; 151: 102907 critrevonc.2020.102907.
  3. Necula L, Matei L, Dragu D, et al. Collagen family as pro- mising biomarkers and therapeutic targets in canc Int J Mol Sci 2022; 23: 12415. 232012415.
  4. Guillaumin J-B, Djerroudi L, Aubry J-F, et al. Proof of concept of 3-D backscatter tensor imaging tomography for non-invasive assessment of human breast cancer col- lagen Ultrasound Med Biol 2022; 48 (9): 1867–78.
  5. Xi G, Qiu L, Xu S, et al. Computer-assisted quantifi ation of tumor-associated collagen signatures to improve the prognosis prediction of breast BMC Med 2021; 19 (1): 273. doi: 10.1186/s12916-021-02146-7.
  6. Angel PA, Zambrzycki Predictive value of collagen in cancer. Adv Cancer Res 2022; 154: 15–45. doi: 10.1016/ bs.acr.2022.02.004.
  7. Zhang J, Liu J, Zhang H, et al. The role of network-forming collagens in cancer Int J cancer 2022, 151 (15): 833–42.  4004.
  8. Rømer AM, Thorseth ML, Hargbøl Immune modulatory properties of collagen in cancer. Front Immunol 2021; 12: 791453. doi: 10.3389/fi 1.791453.
  9. Song K, Yu Z, Zu X, et a Collagen remodeling along cancer progression providing a novel opportunity for cancer diag- nosis and treatment. Int J Mol Sci 2022; 23 (18): 10509.  31810509.
  10. Fang M, Yuan J, Peng Ch, Li Yu. Collagen as a double- edged sword in tumor Tumor Biol 2014; 35 (4): 2871–82. doi: 10.1007/s13277-013-1511-7
  11. Angel PM, Spruill L, Jefferson M, et al. Zonal regulation of collagen-type proteins and posttranslational modifi ations in prostatic benign and cancer tissues by imaging mass spectrometr The prostate 2020; 80 (13): 1071–86. https://
  12. Bodelon C, Mullooly M, Pfeiff RM, et al. Mammary col- lagen architecture and its association with mammographic density and lesion severity among women undergoing im- age-guided breast biopsy. Breast Cancer Res 2021; 23: 105. doi: 11186/s13058-021-01482-z.
  1. Provenzano PP, Eliceiri KW, Campbell JM, et Collagen reorganization at the tumor-stromal interface facilitates lo- cal invasion. BMC Med 2006; 4 (1): 38. doi: 10.1186/1741- 7015-4-38.
  2. Xi G, Guo W, Kang D, et Large-scale tumor-associated collagen signatures identify high-risk breast cancer pa- tients. Theranostics 2021; 11 (7): 3229–43. doi: 10.7150/ thno.55921
  3. Gleason DF, Mellinger GT. Classification of prostatic carci- Cancer Chemother Rep 1966; 50 (3): 125–8.
  4. Epstein JI, Egevad L, Amin MB, et al. The 2014 Interna- tional Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading Am J Surg Pathol 2016; 40 (2): 244–52. doi: 10. 1097/PAS.0000000000000530.
  5. Shah Current perspectives on the Gleason grading of prostate cancer. Arch Pathol Lab Med 2009; 133 (11): 1810–6. doi: 10.5858/133.11.1810.
  6. Garcia AM, Magalhaes FL, Soares JS, et al. Second har- monic generation imaging of the collagen architecture in prostate cancer tissue. Biomed Phys Eng 2018; 4 (2): doi  10.1088/2057-1976/aaa379.
  7. Yavuz BG, Pestana RC, Abugabal YI, et al. Origin and role of hepatic myofi oblasts in hepatocellular carcinoma On- cotarget 2020; 11: 1186–201. https://dorg/10.18632/ oncotarget.27532.
  8. Badaoui M, Mimsy-Julienne C, Saby Ch, et al. Collagen type 1 promotes survival of human breast cancer cells by overexpressing Kv11 potassium and Orai1 calcium chan- nels through DDR1-dependent pathway. Oncotarget 2018; 9 (37): 24653–71. doi: 10.18632/oncotarget.19065.
  9. Zainab H, Sultana A, Stromal desmoplasia as a possible prognostic indicator in different grades of oral squamous cell carcinoma. J Oral Maxillofac Pathol 2019; 23 (3): 338–43. doi: 10.4103/jomfp.JOMFP_136_19.
  10. Taufalele PV, VanderBurgh JA, Muñoz A, et al. Fiber align- ment drives changes in architectural and mechanical features in collagen matrices. PLOS 2019; jopone.0216537.
  11. Gole L, Yeong J, Lim JChT, Ong KH, et al. Quantitative stain-free imaging and digital profi of collagen struc- ture reveal diverse survival of triple negative breast cancer Breast Cancer Research 2020; 22 (1): 42. doi: 10.1186/s13058-020-01282-x.
  12. Ouellette JN, Drifka CR, Pointer KB, et al. Navigating the collagen jungle: the biomedical potential of fi er organi- zation in cancer. Bioengineering (Basel) 2021; 8 (2): 17. doi:  10.3390/bioengineering8020017.

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