DOI: 10.1073/pnas.081626898. Role of tumor–host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors

Role of tumor–host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors

10.1073/pnas.081626898

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The large size of many novel therapeutics impairs their transport through the tumor extracellular matrix and thus limits their therapeutic effectiveness. We propose that extracellular matrix composition, structure, and distribution determine the transport properties in tumors. Furthermore, because the characteristics of the extracellular matrix largely depend on the tumor–host interactions, we postulate that diffusion of macromolecules will vary with tumor type as well as anatomical location. Diffusion coefficients of macromolecules and liposomes in tumors growing in cranial windows (CWs) and dorsal chambers (DCs) were measured by fluorescence recovery after photobleaching. For the same tumor types, diffusion of large molecules was significantly faster in CW than in DC tumors. The greater diffusional hindrance in DC tumors was correlated with higher levels of collagen type I and its organization into fibrils. For molecules with diameters comparable to the interfibrillar space the diffusion was 5- to 10-fold slower in DC than in CW tumors. The slower diffusion in DC tumors was associated with a higher density of host stromal cells that synthesize and organize collagen type I. Our results point to the necessity of developing site-specific drug carriers to improve the delivery of molecular medicine to solid tumors.

Bibliography

Pluen, A., Boucher, Y., Ramanujan, S., McKee, T. D., Gohongi, T., di Tomaso, E., Brown, E. B., Izumi, Y., Campbell, R. B., Berk, D. A., & Jain, R. K. (2001). Role of tumorâhost interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors. Proceedings of the National Academy of Sciences, 98(8), 4628â4633.

Authors 11

Alain Pluen (first)
Yves Boucher (additional)
Saroja Ramanujan (additional)
Trevor D. McKee (additional)
Takeshi Gohongi (additional)
Emmanuelle di Tomaso (additional)
Edward B. Brown (additional)
Yotaro Izumi (additional)
Robert B. Campbell (additional)
David A. Berk (additional)
Rakesh K. Jain (additional)

References 43 Referenced 484

10.1038/nm0698-655
10.1073/pnas.95.8.4607
Y Boucher, L T Baxter, R K Jain Cancer Res 50, 4478–4484 (1990). / Cancer Res by Boucher Y (1990)
10.1073/pnas.96.6.3137
F Yuan, M Dellian, D Fukumura, M Leunig, D A Berk, V P Torchilin, R K Jain Cancer Res 55, 3752–3756 (1995). / Cancer Res by Yuan F (1995)
10.1038/sj.neo.7900056
10.1097/00001622-199905000-00005
P M Gribbon, A Maroudas, K H Parker, C P Winlove Connective Tissue Biology: Integration and Reductionism, eds R K Reed, K Rubin (Portland, London), pp. 95–124 (1998). / Connective Tissue Biology: Integration and Reductionism by Gribbon P M (1998)
10.1113/expphysiol.1987.sp003085
10.1152/physrev.1978.58.1.255
P A Netti, D A Berk, M A Swartz, A J Grodzinsky, R K Jain Cancer Res 60, 2497–2503 (2000). / Cancer Res by Netti P A (2000)
10.1021/ma00130a007
10.1098/rspa.1973.0064
L F Brown, A J Guidi, S J Schnitt, L Van De Water, M L Iruela-Arispe, T K Yeo, K Tognazzi, H F Dvorak Clin Cancer Res 5, 1041–1056 (1999). / Clin Cancer Res by Brown L F (1999)
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10.1146/annurev.bb.09.060180.002343
M Leunig, F Yuan, D Menger, Y Boucher, A F Goetz, K Messmer, R K Jain Cancer Res 52, 6553–6560 (1992). / Cancer Res by Leunig M (1992)
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10.1007/BF01682756
E F Bernstein, L W Fisher, K Li, RG LeBaron, E M Tan, J Uitto Lab Invest 72, 662–669 (1995). / Lab Invest by Bernstein E F (1995)
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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:29 p.m.)
Indexed	2 weeks, 4 days ago (Aug. 5, 2025, 8:42 a.m.)
Issued	24 years, 4 months ago (March 27, 2001)
Published	24 years, 4 months ago (March 27, 2001)
Published Online	24 years, 4 months ago (March 27, 2001)
Published Print	24 years, 4 months ago (April 10, 2001)

Funders 0

None

BibTeX

@article{Pluen_2001, title={Role of tumor–host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.081626898}, DOI={10.1073/pnas.081626898}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Pluen, Alain and Boucher, Yves and Ramanujan, Saroja and McKee, Trevor D. and Gohongi, Takeshi and di Tomaso, Emmanuelle and Brown, Edward B. and Izumi, Yotaro and Campbell, Robert B. and Berk, David A. and Jain, Rakesh K.}, year={2001}, month=mar, pages={4628–4633} }

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  "URL": "http://dx.doi.org/10.1073/pnas.081626898",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2001,
        3,
        27
      ]
    ]
  },
  "assertion": [
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      "label": "Received",
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        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2001-03-27",
      "order": 2,
      "name": "published",
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}