Abstract
Tumor behavior depends on the complex tumor interstitium and microenvironment, which influence transport of fluid and soluble molecules from blood vessels. The purpose of this study was to reveal how complex tumor tissues affect the immunodistribution of serum proteins and time-dependent translocation of bovine serum albumin (BSA) from blood vessels, using relatively differentiated human adenocarcinoma produced by the xenografted A549 cell line. Histological architecture and immunodistribution of the serum proteins in adenocarcinomatous tissues were clearly detected by the in vivo cryotechnique and cryobiopsy. Both albumin and IgG1 were detected in blood vessels, connective tissues around the tumor mass, and the interstitium among tumor cell nests. IgM was mainly detected in blood vessels and connective tissues around the tumor mass but was not detected in the interstitium among the tumor cell nests. At 10 or 30 min after BSA injection, BSA was observed only in blood vessels, but 1 h after the injection, it was also detected in the interstitium and surrounding connective tissues of the tumor mass. The present findings showed topographic variation of molecular permeation in the adenocarcinomatous tumor mass. The interstitial tissues with augmented permeability of serum proteins would increase accessibility of tumor cells to blood-derived molecules.
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Chan FL, Inoue S (1994) Lamina lucida of basement membrane: an artefact. Microsc Res Tech 28:48–59
Shiurba R (2001) Freeze-substitution: origins and applications. Int Rev Cytol 206:45–96
Bignold LP (2003) Pathogenetic mechanisms of nuclear pleomorphism of tumor cells based on the mutator phenotype theory of carcinogenesis. Histol Histopathol 18:657–664
Ohno S, Terada N, Fujii Y, Ueda H, Takayama I (1996) Dynamic structure of glomerular capillary loop as revealed by an in vivo cryotechnique. Virchows Arch 427:519–527
Ohno N, Terada N, Fujii Y, Baba T, Ohno S (2004) “In vivo cryotechnique” for paradigm shift to “living morphology” of animal organs. Biomed Rev 15:1–19
Terada N, Ohno N, Li Z, Fujii Y, Baba T, Ohno S (2006) Application of in vivo cryotechnique to the examination of cells and tissues in living animal organs. Histol Histopathol 21:265–272
Ohno N, Terada N, Saitoh S, Zhou H, Fujii Y, Ohno S (2007) Recent development of in vivo cryotechnique to cryobiopsy for living animals. Histol Histopathol 22:1281–1290
Terada N, Ohno N, Saitoh S, Ohno S (2007) Immunohistochemical detection of hypoxia in mouse liver tissues treated with pimonidazole using “in vivo cryotechnique.” Histochem Cell Biol 128:253–261
Li Z, Ohno N, Terada N, Ohno S (2006) Immunolocalization of serum proteins in living mouse glomeruli under various hemodynamic conditions by “in vivo cryotechnique.” Histochem Cell Biol 126:399–406
Ohno N, Terada N, Ohno S (2006) Histochemical analyses of living mouse liver under different hemodynamic conditions by “in vivo cryotechnique.” Histochem Cell Biol 126:389–398
Jain RK (1987) Transport of molecules in the tumor interstitium: a review. Cancer Res 47:3039–3051
Fukumura D, Jain RK (2007) Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res 74:72–84
Liotta LA, Kohn EC (2001) The microenvironment of the tumor- host interface. Nature (Lond) 411:375–379
Netti PA, Berk DA, Swartz MA, Grodzinsky AJ, Jain RK (2000) Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res 60:2497–2503
Clarijs R, van Dijk M, Ruiter DJ, de Waal RM (2005) Functional and morphologic analysis of the fluid-conducting meshwork in xenografted cutaneous and primary uveal melanoma. Invest Ophthalmol Vis Sci 46:3013–3020
Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A (2006) Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst 98:335–344
Bai Y, Ohno N, Terada N, Saitoh S, Nakazawa T, Nakamura N, Katoh R, Ohno S (2009) Immunolocalization of serum proteins in xenografted mouse model of human tumor cells by various cryotechniques. Histol Histopathol 24:717–728
Sands H, Jones PL, Shah SA, Palme D, Vessella RL, Gallagher BM (1988) Correlation of vascular permeability and blood flow with monoclonal antibody uptake by human Clouser and renal cell xenografts. Cancer Res 48:188–193
Pluen A, Boucher Y, Ramanujan S, McKee TD, Gohongi T, di Tomaso E, Brown EB, Izumi Y, Campbell RB, Berk DA, Jain RK (2001) Role of tumor-host interactions in interstitial diffusion of macromolecules: cranial vs. subcutaneous tumors. Proc Natl Acad Sci U S A 98:4628–4633
Nakamura N, Miyagi E, Murata S, Kawaoi A, Katoh R (2002) Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues. Mod Pathol 15:1058–1067
Ohno N, Terada N, Bai Y, Saitoh S, Nakazawa T, Nakamura N, Naito I, Katoh R, Ohno S (2008) Application of cryobiopsy to morphological and immunohistochemical analyses of xenografted human lung cancer tissues and functional blood vessels. Cancer (Phila) 113:1068–1079
Fujii Y, Ohno N, Li Z, Terada N, Baba T, Ohno S (2006) Morphological and histochemical analyses of living mouse livers by new “cryobiopsy” technique. J Electron Microsc 55:113–122
Chalkley HW (1943) Method for the quantitative morphologic analysis of tissues. J Natl Cancer Inst 4:47–53
Curtis AS (1960) Area and volume measurements by random sampling methods. Med Biol Illus 10:261–266
Mason DY, Biberfeld P (1980) Technical aspects of lymphoma immunohistology. J Histochem Cytochem 28:731–745
Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature (Lond) 432:332–337
Cunha GR, Hayward SW, Wang YZ, Ricke WA (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107:1–10
Jain RK (2001) Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev 46:149–168
Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693
Tilki D, Kilic N, Sevinc S, Zywietz F, Stief CG, Ergun S (2007) Zonespecific remodeling of tumor blood vessels affects tumor growth. Cancer (Phila) 110:2347–2362
Less JR, Posner MC, Boucher Y, Borochovitz D, Wolmark N, Jain RK (1992) Interstitial hypertension in human breast and colorectal tumors. Cancer Res 52:6371–6374
Yang AD, Bauer TW, Camp ER, Somcio R, Liu W, Fan F, Ellis LM (2005) Improving delivery of antineoplastic agents with antivascular endothelial growth factor therapy. Cancer (Phila) 103:1561–1570
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Dr. Y. Bai was a research fellow from the Department of Pathology, Faculty of Medicine, Chifeng University, Inner Mongolia 024000, China, while this work was in progress at the University of Yamanashi.
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Bai, Y., Ohno, N., Terada, N. et al. Differential distribution of blood-derived proteins in xenografted human adenocarcinoma tissues by in vivo cryotechnique and cryobiopsy. Med Mol Morphol 44, 93–102 (2011). https://doi.org/10.1007/s00795-010-0512-5
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DOI: https://doi.org/10.1007/s00795-010-0512-5